rs11964779
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000375750.9(MSH5):c.416-57A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,591,922 control chromosomes in the GnomAD database, including 338 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.027 ( 161 hom., cov: 31)
Exomes 𝑓: 0.0046 ( 177 hom. )
Consequence
MSH5
ENST00000375750.9 intron
ENST00000375750.9 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.668
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 Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MSH5 | NM_172166.4 | c.416-57A>C | intron_variant | ENST00000375750.9 | NP_751898.1 | |||
MSH5-SAPCD1 | NR_037846.1 | n.544-57A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MSH5 | ENST00000375750.9 | c.416-57A>C | intron_variant | 1 | NM_172166.4 | ENSP00000364903 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0271 AC: 4123AN: 152090Hom.: 162 Cov.: 31
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GnomAD4 exome AF: 0.00463 AC: 6667AN: 1439714Hom.: 177 AF XY: 0.00422 AC XY: 3014AN XY: 715046
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GnomAD4 genome AF: 0.0271 AC: 4124AN: 152208Hom.: 161 Cov.: 31 AF XY: 0.0267 AC XY: 1987AN XY: 74424
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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