6-31741276-T-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_172166.4(MSH5):c.261T>G(p.Leu87=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,611,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000052 ( 0 hom. )
Consequence
MSH5
NM_172166.4 synonymous
NM_172166.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0380
Genes affected
MSH5 (HGNC:7328): (mutS homolog 5) This gene encodes a member of the mutS family of proteins that are involved in DNA mismatch repair and meiotic recombination. This protein is similar to a Saccharomyces cerevisiae protein that participates in segregation fidelity and crossing-over events during meiosis. This protein plays a role in promoting ionizing radiation-induced apoptosis. This protein forms hetero-oligomers with another member of this family, mutS homolog 4. Polymorphisms in this gene have been linked to various human diseases, including IgA deficiency, common variable immunodeficiency, and premature ovarian failure. Alternative splicing results multiple transcript variants. Read-through transcription also exists between this gene and the downstream chromosome 6 open reading frame 26 (C6orf26) gene. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 6-31741276-T-G is Benign according to our data. Variant chr6-31741276-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3033693.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.038 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH5 | NM_172166.4 | c.261T>G | p.Leu87= | synonymous_variant | 3/25 | ENST00000375750.9 | |
MSH5-SAPCD1 | NR_037846.1 | n.389T>G | non_coding_transcript_exon_variant | 3/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH5 | ENST00000375750.9 | c.261T>G | p.Leu87= | synonymous_variant | 3/25 | 1 | NM_172166.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000464 AC: 7AN: 151012Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000568 AC: 14AN: 246524Hom.: 0 AF XY: 0.0000893 AC XY: 12AN XY: 134364
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GnomAD4 exome AF: 0.0000520 AC: 76AN: 1460320Hom.: 0 Cov.: 32 AF XY: 0.0000688 AC XY: 50AN XY: 726454
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GnomAD4 genome ? AF: 0.0000464 AC: 7AN: 151012Hom.: 0 Cov.: 31 AF XY: 0.0000407 AC XY: 3AN XY: 73656
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MSH5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 14, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at