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11-65864514-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_025128.5(MUS81):c.1077T>C(p.Cys359=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,614,112 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

MUS81
NM_025128.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-65864514-T-C is Benign according to our data. Variant chr11-65864514-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2641973.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.2 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MUS81NM_025128.5 linkuse as main transcriptc.1077T>C p.Cys359= synonymous_variant 11/16 ENST00000308110.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MUS81ENST00000308110.9 linkuse as main transcriptc.1077T>C p.Cys359= synonymous_variant 11/161 NM_025128.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00136
AC:
207
AN:
152200
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.00150
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00210
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00140
AC:
352
AN:
251412
Hom.:
1
AF XY:
0.00144
AC XY:
196
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.000810
Gnomad ASJ exome
AF:
0.000198
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00192
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00191
AC:
2796
AN:
1461794
Hom.:
6
Cov.:
37
AF XY:
0.00196
AC XY:
1424
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.00110
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00255
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00219
Gnomad4 OTH exome
AF:
0.00119
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00136
AC:
207
AN:
152318
Hom.:
0
Cov.:
33
AF XY:
0.00115
AC XY:
86
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00210
Gnomad4 OTH
AF:
0.00236
Alfa
AF:
0.00149
Hom.:
0
Bravo
AF:
0.00131
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00224
EpiControl
AF:
0.00136

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2022MUS81: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
Cadd
Benign
1.2
Dann
Benign
0.59
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7

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.

Other links and lift over

dbSNP: rs149378507; hg19: chr11-65631985; API