Variant 11-76544410-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001300942.2(EMSY):c.2906T>G(p.Leu969Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000865 in 1,614,060 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 10 hom. )

Consequence

EMSY
NM_001300942.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

EMSY (HGNC:18071): (EMSY transcriptional repressor, BRCA2 interacting) Predicted to enable identical protein binding activity. Predicted to be involved in DNA repair; chromatin organization; and regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

EMSY links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005174011).

BP6

Variant 11-76544410-T-G is Benign according to our data. Variant chr11-76544410-T-G is described in ClinVar as [Benign]. Clinvar id is 712727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 233 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMSY	NM_001300942.2 linkuse as main transcript	c.2906T>G	p.Leu969Arg	missense_variant	20/22	ENST00000695367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMSY	ENST00000695367.1 linkuse as main transcript	c.2906T>G	p.Leu969Arg	missense_variant	20/22		NM_001300942.2		Q7Z589-7

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

228

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00949

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00462

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00251

AC:

631

AN:

251166

Hom.:

AF XY:

0.00195

AC XY:

264

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00430

Gnomad NFE exome

AF:

0.000432

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000796

AC:

1163

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

482

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00360

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00431

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.00153

AC:

233

AN:

152170

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00462

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000345

Hom.:

Bravo

AF:

0.00167

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00195

AC:

237

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0000545

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	Jul 11, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;T;.;.;.;.;T;T

Eigen

Benign

-0.0016

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;D;D;D;D;.;D

MetaRNN

Benign

0.0052

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;.;.;.;.;N;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;N

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N;D

REVEL

Uncertain

0.31

Sift

Benign

0.047

D;D;D;D;D;D;D;D

Sift4G

Benign

0.14

T;T;T;T;T;T;T;T

Polyphen

0.73

P;B;.;.;.;.;B;.

Vest4

0.62

MVP

0.068

MPC

0.46

ClinPred

0.024

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.28

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