rs3753051

Variant names:

• chr11-76546171-T-C
• rs3753051
• NM_001300942.2:c.3693T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-76546171-T-C
• chr11-76546171-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_001300942.2(EMSY):​c.3693T>C​(p.Thr1231Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,613,946 control chromosomes in the GnomAD database, including 74,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.27 (5842 hom., cov: 32)
  • Exomes 𝑓: 0.30 (68731 hom.)
• Consequence: EMSY NM_001300942.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.884
• Publications: 33 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.128).
• BP6: Variant 11-76546171-T-C is Benign according to our data. Variant chr11-76546171-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060664.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.884 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

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.3693T>C	p.Thr1231Thr	synonymous	Exon 21 of 22	NP_001287871.1	Q7Z589-7
	EMSY	NM_001300943.2		c.3651T>C	p.Thr1217Thr	synonymous	Exon 20 of 21	NP_001287872.1	Q7Z589-5
	EMSY	NM_001300944.2		c.3651T>C	p.Thr1217Thr	synonymous	Exon 20 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.3693T>C	p.Thr1231Thr	synonymous	Exon 21 of 22	ENSP00000511840.1	Q7Z589-7
	EMSY	ENST00000524767.5	TSL:1	c.3693T>C	p.Thr1231Thr	synonymous	Exon 20 of 21	ENSP00000433205.1	Q7Z589-7
	EMSY	ENST00000525038.5	TSL:1	c.3651T>C	p.Thr1217Thr	synonymous	Exon 19 of 20	ENSP00000436968.1	Q7Z589-4

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41053 AN: 152010 Hom.: 5838 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.267 AC: 67132 AN: 251174 AF XY: 0.271

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.389

Gnomad EAS exome AF: 0.122

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.290

GnomAD4 exome AF: 0.302 AC: 441176 AN: 1461818 Hom.: 68731 Cov.: 40 AF XY: 0.301 AC XY: 219014 AN XY: 727200

African (AFR) AF: 0.203 AC: 6809 AN: 33480

American (AMR) AF: 0.159 AC: 7089 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 10217 AN: 26136

East Asian (EAS) AF: 0.138 AC: 5494 AN: 39680

South Asian (SAS) AF: 0.242 AC: 20847 AN: 86258

European-Finnish (FIN) AF: 0.326 AC: 17394 AN: 53418

Middle Eastern (MID) AF: 0.300 AC: 1729 AN: 5768

European-Non Finnish (NFE) AF: 0.318 AC: 353871 AN: 1111966

Other (OTH) AF: 0.294 AC: 17726 AN: 60392

GnomAD4 genome AF: 0.270 AC: 41060 AN: 152128 Hom.: 5842 Cov.: 32 AF XY: 0.269 AC XY: 19993 AN XY: 74358

African (AFR) AF: 0.209 AC: 8684 AN: 41514

American (AMR) AF: 0.206 AC: 3144 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1327 AN: 3468

East Asian (EAS) AF: 0.128 AC: 663 AN: 5178

South Asian (SAS) AF: 0.230 AC: 1107 AN: 4818

European-Finnish (FIN) AF: 0.338 AC: 3573 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21487 AN: 67982

Other (OTH) AF: 0.278 AC: 588 AN: 2114

Alfa AF: 0.300 Hom.: 5422

Bravo AF: 0.259

Asia WGS AF: 0.189 AC: 658 AN: 3478

EpiCase AF: 0.318

EpiControl AF: 0.312

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EMSY-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.4
DANN	Benign	0.63
PhyloP100		0.88
PromoterAI		0.033	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs3753051; hg19: chr11-76257215; COSMIC: COSV58258432; COSMIC: COSV58258432;