6-85471336-C-A

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1PP5

The NM_002526.4(NT5E):c.662C>A(p.Ser221*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000391 in 1,612,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

NT5E
NM_002526.4 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.09

Publications

14 publications found

Variant links:

Genes affected

NT5E (HGNC:8021): (5'-nucleotidase ecto) The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

NT5E Gene-Disease associations (from GenCC):

hereditary arterial and articular multiple calcification syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

NT5E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 6-85471336-C-A is Pathogenic according to our data. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85471336-C-A is described in CliVar as Pathogenic. Clinvar id is 29687.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5E	NM_002526.4 link	c.662C>A	p.Ser221*	stop_gained	Exon 3 of 9	ENST00000257770.8	NP_002517.1	P21589-1Q6NZX3
NT5E	NM_001204813.2 link	c.662C>A	p.Ser221*	stop_gained	Exon 3 of 8		NP_001191742.1	P21589-2Q6NZX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NT5E	ENST00000257770.8 link	c.662C>A	p.Ser221*	stop_gained	Exon 3 of 9	1	NM_002526.4	ENSP00000257770.3	P21589-1
NT5E	ENST00000369646.7 link	c.662C>A	p.Ser221*	stop_gained	Exon 3 of 3	1		ENSP00000358660.3	Q96B60
NT5E	ENST00000369651.7 link	c.662C>A	p.Ser221*	stop_gained	Exon 3 of 8	2		ENSP00000358665.3	P21589-2
NT5E	ENST00000416334.5 link	c.-47C>A		upstream_gene_variant		3		ENSP00000414674.1	H0Y7R7

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000318

AC:

AN:

251184

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1460894

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726750

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

1111324

Other (OTH)

AF:

0.0000331

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.000138

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

41404

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000878

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hereditary arterial and articular multiple calcification syndrome

Pathogenic:1

Feb 03, 2011

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

PhyloP100

7.1

Vest4

0.80

GERP RS

4.9

PromoterAI

-0.092

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=0/200

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over