Variant 11-65864791-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000308110.9(MUS81):c.1248G>T(p.Thr416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,612,924 control chromosomes in the GnomAD database, including 328,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23672 hom., cov: 33)

Exomes 𝑓: 0.64 ( 304820 hom. )

Consequence

MUS81
ENST00000308110.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -9.37

Variant links:

Genes affected

MUS81 (HGNC:29814): (MUS81 structure-specific endonuclease subunit) This gene encodes a structure-specific endonuclease which belongs to the XPF/MUS81 endonuclease family and plays a critical role in the resolution of recombination intermediates during DNA repair after inter-strand cross-links, replication fork collapse, and DNA double-strand breaks. The encoded protein associates with one of two closely related essential meiotic endonuclease proteins (EME1 or EME2) to form a complex that processes DNA secondary structures. It contains an N-terminal DEAH helicase domain, an excision repair cross complementation group 4 (ERCC4) endonuclease domain, and two tandem C-terminal helix-hairpin-helix domains. Mice with a homozygous knockout of the orthologous gene have significant meiotic defects including the failure to repair a subset of DNA double strand breaks. [provided by RefSeq, Jun 2017]

MUS81 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-65864791-G-T is Benign according to our data. Variant chr11-65864791-G-T is described in ClinVar as [Benign]. Clinvar id is 402819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-9.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUS81	NM_025128.5 linkuse as main transcript	c.1248G>T	p.Thr416=	synonymous_variant	12/16	ENST00000308110.9	NP_079404.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUS81	ENST00000308110.9 linkuse as main transcript	c.1248G>T	p.Thr416=	synonymous_variant	12/16	1	NM_025128.5	ENSP00000307853	P1

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

79843

AN:

151936

Hom.:

23677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.704

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.573

AC:

143491

AN:

250230

Hom.:

44315

AF XY:

0.595

AC XY:

80586

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.251

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.636

Gnomad EAS exome

AF:

0.320

Gnomad SAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.703

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.619

GnomAD4 exome

AF:

0.638

AC:

932128

AN:

1460870

Hom.:

304820

Cov.:

AF XY:

0.641

AC XY:

465888

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.636

Gnomad4 EAS exome

AF:

0.323

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.701

Gnomad4 NFE exome

AF:

0.669

Gnomad4 OTH exome

AF:

0.618

GnomAD4 genome

AF:

0.525

AC:

79850

AN:

152054

Hom.:

23672

Cov.:

AF XY:

0.528

AC XY:

39262

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.639

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.620

Gnomad4 FIN

AF:

0.706

Gnomad4 NFE

AF:

0.671

Gnomad4 OTH

AF:

0.559

Alfa

AF:

0.633

Hom.:

37182

Bravo

AF:

0.492

Asia WGS

AF:

0.490

AC:

1705

AN:

3478

EpiCase

AF:

0.680

EpiControl

AF:

0.688

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.057

DANN

Benign

0.82

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over