rs1954782

Variant names:

• chr11-76516261-A-C
• rs1954782
• NM_001300942.2:c.1678A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001300942.2(EMSY):​c.1678A>C​(p.Lys560Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 8.62
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMSY	NM_001300942.2	MANE Select	c.1678A>C	p.Lys560Gln	missense	Exon 12 of 22	NP_001287871.1	Q7Z589-7
	EMSY	NM_001300943.2		c.1636A>C	p.Lys546Gln	missense	Exon 11 of 21	NP_001287872.1	Q7Z589-5
	EMSY	NM_001300944.2		c.1678A>C	p.Lys560Gln	missense	Exon 12 of 21	NP_001287873.1	Q7Z589-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMSY	ENST00000695367.1	MANE Select	c.1678A>C	p.Lys560Gln	missense	Exon 12 of 22	ENSP00000511840.1	Q7Z589-7
	EMSY	ENST00000524767.5	TSL:1	c.1678A>C	p.Lys560Gln	missense	Exon 11 of 21	ENSP00000433205.1	Q7Z589-7
	EMSY	ENST00000525038.5	TSL:1	c.1678A>C	p.Lys560Gln	missense	Exon 11 of 20	ENSP00000436968.1	Q7Z589-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0029	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.69	N
PhyloP100		8.6
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.059	T
Polyphen		1.0	D
Vest4		0.52
MutPred		0.42		Loss of ubiquitination at K545 (P = 0.0134)
MVP		0.29
MPC		1.3
ClinPred		0.94	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.86
Mutation Taster		=72/28	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: rs1954782; hg19: chr11-76227305;