rs2229523

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002526.4(NT5E):c.1126A>G(p.Thr376Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 1,611,060 control chromosomes in the GnomAD database, including 397,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.76 ( 45429 hom., cov: 31)

Exomes 𝑓: 0.69 ( 351778 hom. )

Consequence

NT5E
NM_002526.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter U:1B:3

Conservation

PhyloP100: -0.0450

Publications

54 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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.6498304E-7).

BP6

Variant 6-85489515-A-G is Benign according to our data. Variant chr6-85489515-A-G is described in ClinVar as Benign. ClinVar VariationId is 1175159.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5E	NM_002526.4 link	c.1126A>G	p.Thr376Ala	missense_variant	Exon 6 of 9	ENST00000257770.8	NP_002517.1	P21589-1Q6NZX3
NT5E	NM_001204813.2 link	c.1126A>G	p.Thr376Ala	missense_variant	Exon 6 of 8		NP_001191742.1	P21589-2Q6NZX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NT5E	ENST00000257770.8 link	c.1126A>G	p.Thr376Ala	missense_variant	Exon 6 of 9	1	NM_002526.4	ENSP00000257770.3	P21589-1
NT5E	ENST00000369651.7 link	c.1126A>G	p.Thr376Ala	missense_variant	Exon 6 of 8	2		ENSP00000358665.3	P21589-2
NT5E	ENST00000416334.5 link	c.418A>G	p.Thr140Ala	missense_variant	Exon 4 of 5	3		ENSP00000414674.1	H0Y7R7
NT5E	ENST00000437581.1 link	c.211A>G	p.Thr71Ala	missense_variant	Exon 3 of 5	3		ENSP00000387630.1	H0Y3X5

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

115955

AN:

151954

Hom.:

45368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.927

Gnomad AMI

AF:

0.802

Gnomad AMR

AF:

0.823

Gnomad ASJ

AF:

0.762

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.834

Gnomad FIN

AF:

0.631

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.752

GnomAD2 exomes

AF:

0.732

AC:

183773

AN:

250940

AF XY:

0.730

show subpopulations

Gnomad AFR exome

AF:

0.934

Gnomad AMR exome

AF:

0.869

Gnomad ASJ exome

AF:

0.768

Gnomad EAS exome

AF:

0.594

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.675

Gnomad OTH exome

AF:

0.723

GnomAD4 exome

AF:

0.690

AC:

1006827

AN:

1458986

Hom.:

351778

Cov.:

AF XY:

0.693

AC XY:

503263

AN XY:

725922

show subpopulations

African (AFR)

AF:

0.933

AC:

31158

AN:

33412

American (AMR)

AF:

0.863

AC:

38584

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.766

AC:

20007

AN:

26122

East Asian (EAS)

AF:

0.605

AC:

24008

AN:

39656

South Asian (SAS)

AF:

0.835

AC:

71998

AN:

86204

European-Finnish (FIN)

AF:

0.625

AC:

33349

AN:

53366

Middle Eastern (MID)

AF:

0.812

AC:

4673

AN:

5758

European-Non Finnish (NFE)

AF:

0.667

AC:

739901

AN:

1109468

Other (OTH)

AF:

0.716

AC:

43149

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

15523

31046

46568

62091

77614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19256

38512

57768

77024

96280

<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:

0.763

AC:

116079

AN:

152074

Hom.:

45429

Cov.:

AF XY:

0.763

AC XY:

56754

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.927

AC:

38503

AN:

41518

American (AMR)

AF:

0.823

AC:

12575

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.762

AC:

2646

AN:

3472

East Asian (EAS)

AF:

0.603

AC:

3113

AN:

5164

South Asian (SAS)

AF:

0.834

AC:

4016

AN:

4816

European-Finnish (FIN)

AF:

0.631

AC:

6662

AN:

10560

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.677

AC:

45996

AN:

67944

Other (OTH)

AF:

0.753

AC:

1593

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1318

2636

3954

5272

6590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.707

Hom.:

154685

Bravo

AF:

0.783

TwinsUK

AF:

0.655

AC:

2427

ALSPAC

AF:

0.652

AC:

2514

ESP6500AA

AF:

0.925

AC:

4075

ESP6500EA

AF:

0.692

AC:

5955

ExAC

AF:

0.734

AC:

89061

Asia WGS

AF:

0.740

AC:

2572

AN:

3478

EpiCase

AF:

0.691

EpiControl

AF:

0.698

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary arterial and articular multiple calcification syndrome

Uncertain:1Benign:1

Jan 01, 2022

Sayed Lab, Stanford University

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.22

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.082

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.022

T;T

MetaRNN

Benign

7.6e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

N;N

PhyloP100

-0.045

PrimateAI

Benign

0.23

PROVEAN

Benign

0.79

N;N

REVEL

Benign

0.059

Sift

Benign

0.52

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0

.;B

Vest4

0.050

MPC

0.17

ClinPred

0.00026

GERP RS

-0.40

Varity_R

0.085

gMVP

0.65

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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