Genetic Variant EMSY:p.Thr1231Thr (chr11-76546171-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.884

Publications

33 publications found

Variant links:

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]

EMSY links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMSY	NM_001300942.2 link	c.3693T>C	p.Thr1231Thr	synonymous_variant	Exon 21 of 22	ENST00000695367.1	NP_001287871.1	Q7Z589-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMSY	ENST00000695367.1 link	c.3693T>C	p.Thr1231Thr	synonymous_variant	Exon 21 of 22		NM_001300942.2	ENSP00000511840.1		Q7Z589-7

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41053

AN:

152010

Hom.:

5838

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.301

AC XY:

219014

AN XY:

727200

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

19058

38116

57174

76232

95290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.270

AC:

41060

AN:

152128

Hom.:

5842

Cov.:

AF XY:

0.269

AC XY:

19993

AN XY:

74358

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21487

AN:

67982

Other (OTH)

AF:

0.278

AC:

588

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1509

3018

4527

6036

7545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EMSY-related disorder

Benign:1

Oct 27, 2021

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.4

(source)

DANN

Benign

0.63

PhyloP100

0.88

PromoterAI

0.033

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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11-76546171-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over