Variant chr15-29268942-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_138704.4(NSMCE3):c.764A>T(p.Asn255Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,614,172 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 32 hom. )

Consequence

NSMCE3
NM_138704.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.170

Variant links:

Genes affected

NSMCE3 (HGNC:7677): (NSE3 homolog, SMC5-SMC6 complex component) The protein encoded by this gene is part of the SMC5-6 chromatin reorganizing complex and is a member of the MAGE superfamily. This is an intronless gene. [provided by RefSeq, May 2011]

NSMCE3 links:

ENTREP2 (HGNC:29075): (endosomal transmembrane epsin interactor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTREP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007313907).

BP6

Variant 15-29268942-T-A is Benign according to our data. Variant chr15-29268942-T-A is described in ClinVar as [Benign]. Clinvar id is 710048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1584/152278) while in subpopulation AFR AF= 0.036 (1497/41560). AF 95% confidence interval is 0.0345. There are 27 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSMCE3	NM_138704.4 linkuse as main transcript	c.764A>T	p.Asn255Ile	missense_variant	1/1	ENST00000332303.6
ENTREP2	NM_015307.2 linkuse as main transcript	c.277-16464A>T		intron_variant		ENST00000261275.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSMCE3	ENST00000332303.6 linkuse as main transcript	c.764A>T	p.Asn255Ile	missense_variant	1/1		NM_138704.4	P1
ENTREP2	ENST00000261275.5 linkuse as main transcript	c.277-16464A>T		intron_variant		5	NM_015307.2	P1	O60320-1
ENTREP2	ENST00000560082.1 linkuse as main transcript	c.-12-16464A>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1577

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00816

GnomAD3 exomes

AF:

0.00262

AC:

659

AN:

251474

Hom.:

AF XY:

0.00189

AC XY:

257

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0359

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00108

AC:

1575

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

669

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0392

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00225

GnomAD4 genome

AF:

0.0104

AC:

1584

AN:

152278

Hom.:

Cov.:

AF XY:

0.00967

AC XY:

720

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0360

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00807

Alfa

AF:

0.00541

Hom.:

Bravo

AF:

0.0118

ESP6500AA

AF:

0.0370

AC:

163

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00313

AC:

380

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.058

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.8

REVEL

Benign

0.083

Sift

Benign

0.33

Sift4G

Benign

0.42

Polyphen

0.45

Vest4

0.39

MVP

0.40

MPC

0.57

ClinPred

0.014

GERP RS

0.36

Varity_R

0.35

gMVP

0.44

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