chr11-76546251-T-C

Variant names:

• chr11-76546251-T-C
• rs1047196
• NM_001300942.2:c.3773T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/20 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
• Publications: 4 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300942.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMSY	NM_001300942.2	MANE Select	c.3773T>C	p.Val1258Ala	missense	Exon 21 of 22	NP_001287871.1
	EMSY	NM_001300943.2		c.3731T>C	p.Val1244Ala	missense	Exon 20 of 21	NP_001287872.1
	EMSY	NM_001300944.2		c.3731T>C	p.Val1244Ala	missense	Exon 20 of 21	NP_001287873.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMSY	ENST00000695367.1	MANE Select	c.3773T>C	p.Val1258Ala	missense	Exon 21 of 22	ENSP00000511840.1
	EMSY	ENST00000524767.5	TSL:1	c.3773T>C	p.Val1258Ala	missense	Exon 20 of 21	ENSP00000433205.1
	EMSY	ENST00000525038.5	TSL:1	c.3731T>C	p.Val1244Ala	missense	Exon 19 of 20	ENSP00000436968.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.9
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.54	T
Polyphen		0.034	B
Vest4		0.14
MutPred		0.23		Loss of stability (P = 0.0271)
MVP		0.043
MPC		0.077
ClinPred		0.50	D
GERP RS		6.1
PromoterAI		0.028	Neutral
Varity_R		0.064
gMVP		0.57
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1047196; hg19: chr11-76257295;