rs530211997

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015450.3(POT1):​c.*998G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

POT1
NM_015450.3 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.502

Publications

2 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POT1NM_015450.3 linkc.*998G>T 3_prime_UTR_variant Exon 19 of 19 ENST00000357628.8 NP_056265.2 Q9NUX5-1A0A024R739

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POT1ENST00000357628.8 linkc.*998G>T 3_prime_UTR_variant Exon 19 of 19 2 NM_015450.3 ENSP00000350249.3 Q9NUX5-1
POT1ENST00000393329.5 linkc.*998G>T 3_prime_UTR_variant Exon 18 of 18 5 ENSP00000377002.1 A8MTK3
POT1ENST00000430927.6 linkn.*425-413G>T intron_variant Intron 18 of 18 3 ENSP00000397632.2 Q5MJ34
POT1ENST00000436534.5 linkn.392-413G>T intron_variant Intron 4 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152038
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
13844
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
7354
African (AFR)
AF:
0.00
AC:
0
AN:
536
American (AMR)
AF:
0.00
AC:
0
AN:
2100
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
402
East Asian (EAS)
AF:
0.00
AC:
0
AN:
1566
South Asian (SAS)
AF:
0.00
AC:
0
AN:
1432
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
392
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
20
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
6898
Other (OTH)
AF:
0.00
AC:
0
AN:
498
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152038
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74274
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41390
American (AMR)
AF:
0.0000655
AC:
1
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3462
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67962
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.29
DANN
Benign
0.60
PhyloP100
-0.50
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs530211997; hg19: chr7-124463018; API