11-76544468-G-C

Position:

• chr11-76544468-G-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.2964G>C​(p.Gln988His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q988Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMSY NM_001300942.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53

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=0.1832565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMSY	NM_001300942.2	c.2964G>C	p.Gln988His	missense_variant	20/22	ENST00000695367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMSY	ENST00000695367.1	c.2964G>C	p.Gln988His	missense_variant	20/22		NM_001300942.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T;T;.;.;.;.;T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;.;D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.69	.;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	Benign	0.18
Sift	Uncertain	0.0070	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.033	D;D;D;T;D;D;D;T
Polyphen		0.99	D;B;.;.;.;.;B;.
Vest4		0.43
MutPred		0.11		.;Loss of ubiquitination at K977 (P = 0.0561);.;.;.;.;Loss of ubiquitination at K977 (P = 0.0561);.;
MVP		0.21
MPC		0.37
ClinPred		0.65	D
GERP RS		5.0
Varity_R		0.24
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-76255512;