Variant 6-85467177-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002526.4(NT5E):c.457C>G(p.Gln153Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000548 in 1,614,148 control chromosomes in the GnomAD database, including 1 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 0.00087 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 1 hom. )

Consequence

NT5E
NM_002526.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.61

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0041484237).

BP6

Variant 6-85467177-C-G is Benign according to our data. Variant chr6-85467177-C-G is described in ClinVar as [Benign]. Clinvar id is 760697.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5E	NM_002526.4 linkuse as main transcript	c.457C>G	p.Gln153Glu	missense_variant	2/9	ENST00000257770.8	NP_002517.1	P21589-1Q6NZX3
NT5E	NM_001204813.2 linkuse as main transcript	c.457C>G	p.Gln153Glu	missense_variant	2/8		NP_001191742.1	P21589-2Q6NZX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NT5E	ENST00000257770.8 linkuse as main transcript	c.457C>G	p.Gln153Glu	missense_variant	2/9	1	NM_002526.4	ENSP00000257770.3	P21589-1
NT5E	ENST00000369646.7 linkuse as main transcript	c.457C>G	p.Gln153Glu	missense_variant	2/3	1		ENSP00000358660.3	Q96B60
NT5E	ENST00000369651.7 linkuse as main transcript	c.457C>G	p.Gln153Glu	missense_variant	2/8	2		ENSP00000358665.3	P21589-2

Frequencies

GnomAD3 genomes

AF:

0.000874

AC:

133

AN:

152174

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:

0.00698

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000852

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00101

AC:

253

AN:

251342

Hom.:

AF XY:

0.000994

AC XY:

135

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00698

Gnomad NFE exome

AF:

0.000836

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000514

AC:

752

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000534

AC XY:

388

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00588

Gnomad4 NFE exome

AF:

0.000367

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000873

AC:

133

AN:

152292

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00698

Gnomad4 NFE

AF:

0.000852

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000567

Hom.:

Bravo

AF:

0.000336

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000914

AC:

111

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NT5E-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.27

.;.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;.;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.14

N;N;N

REVEL

Benign

0.065

Sift

Benign

0.64

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010, 0.0

.;B;B

Vest4

0.16

MVP

0.34

MPC

0.19

ClinPred

0.010

GERP RS

3.8

Varity_R

0.11

gMVP

0.73

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over