rs1224859801

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_015450.3(POT1):c.996A>G(p.Leu332Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,600,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L332L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

POT1
NM_015450.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.686

Publications

0 publications found

Variant links:

Genes affected

POT1 (HGNC:17284): (protection of telomeres 1) This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein functions as a member of a multi-protein complex that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. Increased transcriptional expression of this gene is associated with stomach carcinogenesis and its progression. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

POT1 Gene-Disease associations (from GenCC):

pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
tumor predisposition syndrome 3
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
glioma susceptibility 9
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
thyroid gland carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
cerebroretinal microangiopathy with calcifications and cysts 3
Inheritance: AR Classification: LIMITED Submitted by: G2P, Ambry Genetics

POT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 7-124846952-T-C is Benign according to our data. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-124846952-T-C is described in CliVar as Likely_benign. Clinvar id is 541884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.686 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POT1	NM_015450.3 link	c.996A>G	p.Leu332Leu	synonymous_variant	Exon 12 of 19	ENST00000357628.8	NP_056265.2	Q9NUX5-1A0A024R739

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POT1	ENST00000357628.8 link	c.996A>G	p.Leu332Leu	synonymous_variant	Exon 12 of 19	2	NM_015450.3	ENSP00000350249.3		Q9NUX5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1448558

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721542

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33146

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39588

South Asian (SAS)

AF:

0.00

AC:

AN:

85920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000454

AC:

AN:

1100158

Other (OTH)

AF:

0.00

AC:

AN:

59946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tumor predisposition syndrome 3

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Dec 21, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.4

(source)

DANN

Benign

0.78

PhyloP100

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over