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GeneBe

11-76544676-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001300942.2(EMSY):ā€‹c.3172G>Cā€‹(p.Val1058Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

EMSY
NM_001300942.2 missense

Scores

2
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2
Missense variant where missense usually causes diseases, EMSY
BP4
Computational evidence support a benign effect (MetaRNN=0.13651657).
BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EMSYNM_001300942.2 linkuse as main transcriptc.3172G>C p.Val1058Leu missense_variant 20/22 ENST00000695367.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EMSYENST00000695367.1 linkuse as main transcriptc.3172G>C p.Val1058Leu missense_variant 20/22 NM_001300942.2 Q7Z589-7

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
251108
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135742
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000313
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 18, 2021The c.3127G>C (p.V1043L) alteration is located in exon 19 (coding exon 18) of the EMSY gene. This alteration results from a G to C substitution at nucleotide position 3127, causing the valine (V) at amino acid position 1043 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.55
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.022
T;T;.;.;.;.;T;T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D;.;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.14
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D
PROVEAN
Benign
-0.83
N;N;N;N;N;N;N;N
REVEL
Benign
0.23
Sift
Benign
0.036
D;D;D;D;D;D;D;D
Sift4G
Benign
0.17
T;T;T;T;T;T;T;D
Polyphen
0.98
D;P;.;.;.;.;P;.
Vest4
0.62
MutPred
0.086
.;Loss of glycosylation at T1042 (P = 0.0994);.;.;.;.;Loss of glycosylation at T1042 (P = 0.0994);.;
MVP
0.27
MPC
0.30
ClinPred
0.20
T
GERP RS
5.5
Varity_R
0.20
gMVP
0.38

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.

Other links and lift over

dbSNP: rs752877805; hg19: chr11-76255720; API