dbSNP rs777034208: MUS81:p.Arg293Gly (chr11-65863637-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025128.5(MUS81):c.877C>G(p.Arg293Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R293W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MUS81
NM_025128.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

2 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2579906).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025128.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MUS81	NM_025128.5	MANE Select	c.877C>G	p.Arg293Gly	missense	Exon 9 of 16	NP_079404.3
MUS81	NM_001350283.2		c.877C>G	p.Arg293Gly	missense	Exon 9 of 16	NP_001337212.1
MUS81	NR_146598.2		n.1198C>G		non_coding_transcript_exon	Exon 9 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUS81	ENST00000308110.9	TSL:1 MANE Select	c.877C>G	p.Arg293Gly	missense	Exon 9 of 16	ENSP00000307853.4	Q96NY9
MUS81	ENST00000907324.1		c.877C>G	p.Arg293Gly	missense	Exon 11 of 18	ENSP00000577383.1
MUS81	ENST00000971503.1		c.877C>G	p.Arg293Gly	missense	Exon 10 of 17	ENSP00000641562.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Benign

0.083

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.79

M_CAP

Benign

0.011

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.6

PhyloP100

1.1

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.073

Sift

Uncertain

0.0060

Sift4G

Benign

0.14

Polyphen

0.090

Vest4

0.39

MutPred

0.52

Loss of solvent accessibility (P = 0.0044)

MVP

0.40

MPC

0.17

ClinPred

0.96

GERP RS

3.3

Varity_R

0.68

gMVP

0.55

Mutation Taster

=46/54

disease causing

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over