Variant 6-85489525-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002526.4(NT5E):c.1136T>C(p.Met379Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0769 in 1,612,932 control chromosomes in the GnomAD database, including 8,596 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 3178 hom., cov: 32)

Exomes 𝑓: 0.069 ( 5418 hom. )

Consequence

NT5E
NM_002526.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.682

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028433502).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5E	NM_002526.4 linkuse as main transcript	c.1136T>C	p.Met379Thr	missense_variant	6/9	ENST00000257770.8
NT5E	NM_001204813.2 linkuse as main transcript	c.1136T>C	p.Met379Thr	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5E	ENST00000257770.8 linkuse as main transcript	c.1136T>C	p.Met379Thr	missense_variant	6/9	1	NM_002526.4	P1	P21589-1
NT5E	ENST00000369651.7 linkuse as main transcript	c.1136T>C	p.Met379Thr	missense_variant	6/8	2			P21589-2
NT5E	ENST00000416334.5 linkuse as main transcript	c.431T>C	p.Met144Thr	missense_variant	4/5	3
NT5E	ENST00000437581.1 linkuse as main transcript	c.224T>C	p.Met75Thr	missense_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22970

AN:

151988

Hom.:

3171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0987

Gnomad ASJ

AF:

0.0878

Gnomad EAS

AF:

0.0525

Gnomad SAS

AF:

0.0942

Gnomad FIN

AF:

0.0597

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0610

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.0851

AC:

21367

AN:

251136

Hom.:

1719

AF XY:

0.0810

AC XY:

10999

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.0558

Gnomad ASJ exome

AF:

0.0847

Gnomad EAS exome

AF:

0.0647

Gnomad SAS exome

AF:

0.0814

Gnomad FIN exome

AF:

0.0590

Gnomad NFE exome

AF:

0.0618

Gnomad OTH exome

AF:

0.0721

GnomAD4 exome

AF:

0.0692

AC:

101017

AN:

1460826

Hom.:

5418

Cov.:

AF XY:

0.0687

AC XY:

49950

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.0602

Gnomad4 ASJ exome

AF:

0.0892

Gnomad4 EAS exome

AF:

0.0526

Gnomad4 SAS exome

AF:

0.0799

Gnomad4 FIN exome

AF:

0.0580

Gnomad4 NFE exome

AF:

0.0590

Gnomad4 OTH exome

AF:

0.0853

GnomAD4 genome

AF:

0.151

AC:

23011

AN:

152106

Hom.:

3178

Cov.:

AF XY:

0.148

AC XY:

10990

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.371

Gnomad4 AMR

AF:

0.0985

Gnomad4 ASJ

AF:

0.0878

Gnomad4 EAS

AF:

0.0527

Gnomad4 SAS

AF:

0.0928

Gnomad4 FIN

AF:

0.0597

Gnomad4 NFE

AF:

0.0610

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.0774

Hom.:

1247

Bravo

AF:

0.163

TwinsUK

AF:

0.0612

AC:

227

ALSPAC

AF:

0.0576

AC:

222

ESP6500AA

AF:

0.364

AC:

1603

ESP6500EA

AF:

0.0685

AC:

589

ExAC

AF:

0.0909

AC:

11036

Asia WGS

AF:

0.0790

AC:

276

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.67

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.42

T;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.38

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.062

Sift

Benign

0.61

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0

.;B

Vest4

0.095

MPC

0.20

ClinPred

0.0021

GERP RS

-0.33

Varity_R

0.068

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over