rs1047196

Positions:

• chr11-76546251-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001300942.2(EMSY):​c.3773T>C​(p.Val1258Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMSY NM_001300942.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15692794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMSY	NM_001300942.2	c.3773T>C	p.Val1258Ala	missense_variant	21/22	ENST00000695367.1	NP_001287871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMSY	ENST00000695367.1	c.3773T>C	p.Val1258Ala	missense_variant	21/22		NM_001300942.2	ENSP00000511840

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T;T;.;.;.;.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;.
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.55	.;N;.;.;.;.;N
MutationTaster	Benign	0.95	D;D;D;D;D;D;D;D
PROVEAN	Benign	-0.42	N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D;D;D;D;D;D;D
Sift4G	Benign	0.54	T;T;T;T;T;T;T
Polyphen		0.034	B;B;.;.;.;.;B
Vest4		0.14
MutPred		0.23		.;Loss of stability (P = 0.0271);.;.;.;.;Loss of stability (P = 0.0271);
MVP		0.043
MPC		0.077
ClinPred		0.50	D
GERP RS		6.1
Varity_R		0.064
gMVP		0.57

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

Other links and lift over

dbSNP: rs1047196; hg19: chr11-76257295;