dbSNP rs630303: MUS81:p.Arg355Arg (chr11-65864502-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_025128.5(MUS81):c.1065G>A(p.Arg355Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,612,680 control chromosomes in the GnomAD database, including 328,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23703 hom., cov: 32)

Exomes 𝑓: 0.64 ( 304880 hom. )

Consequence

MUS81
NM_025128.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0300

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=-0.73).

BP6

Variant 11-65864502-G-A is Benign according to our data. Variant chr11-65864502-G-A is described in ClinVar as [Benign]. Clinvar id is 402818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.03 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 rank	MANE	Protein	UniProt
MUS81	NM_025128.5 link	c.1065G>A	p.Arg355Arg	synonymous_variant	Exon 11 of 16	ENST00000308110.9	NP_079404.3	Q96NY9Q53ES5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUS81	ENST00000308110.9 link	c.1065G>A	p.Arg355Arg	synonymous_variant	Exon 11 of 16	1	NM_025128.5	ENSP00000307853.4		Q96NY9

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

79956

AN:

151964

Hom.:

23708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

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:

0.705

Gnomad MID

AF:

0.704

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.560

GnomAD3 exomes

AF:

0.574

AC:

144193

AN:

251210

Hom.:

44551

AF XY:

0.596

AC XY:

80887

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.636

Gnomad EAS exome

AF:

0.320

Gnomad SAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.618

GnomAD4 exome

AF:

0.638

AC:

932091

AN:

1460598

Hom.:

304880

Cov.:

AF XY:

0.641

AC XY:

465843

AN XY:

726666

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.379

Gnomad4 ASJ exome

AF:

0.636

Gnomad4 EAS exome

AF:

0.323

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.700

Gnomad4 NFE exome

AF:

0.669

Gnomad4 OTH exome

AF:

0.619

GnomAD4 genome

AF:

0.526

AC:

79968

AN:

152082

Hom.:

23703

Cov.:

AF XY:

0.529

AC XY:

39331

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.639

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.620

Gnomad4 FIN

AF:

0.705

Gnomad4 NFE

AF:

0.671

Gnomad4 OTH

AF:

0.560

Alfa

AF:

0.631

Hom.:

44789

Bravo

AF:

0.492

Asia WGS

AF:

0.490

AC:

1708

AN:

3478

EpiCase

AF:

0.680

EpiControl

AF:

0.690

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.1

DANN

Benign

0.85

RBP_binding_hub_radar

0.97

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