rs17207454
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000375755.8(MSH5):c.-47C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000932 in 370,114 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00068 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 0 hom. )
Consequence
MSH5
ENST00000375755.8 5_prime_UTR
ENST00000375755.8 5_prime_UTR
Scores
2
Splicing: ADA: 0.00008007
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0280
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 -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH5 | NM_172166.4 | c.-14+125C>T | intron_variant | ENST00000375750.9 | |||
MSH5-SAPCD1 | NR_037846.1 | n.115+125C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH5 | ENST00000375750.9 | c.-14+125C>T | intron_variant | 1 | NM_172166.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000684 AC: 104AN: 152012Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00111 AC: 241AN: 217984Hom.: 0 Cov.: 3 AF XY: 0.00108 AC XY: 122AN XY: 112704
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GnomAD4 genome ? AF: 0.000684 AC: 104AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.000511 AC XY: 38AN XY: 74374
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at