rs5742981
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000534.5(PMS1):c.315+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 1,578,098 control chromosomes in the GnomAD database, including 1,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.031 ( 113 hom., cov: 32)
Exomes 𝑓: 0.036 ( 1123 hom. )
Consequence
PMS1
NM_000534.5 splice_donor_region, intron
NM_000534.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001624
2
Clinical Significance
Conservation
PhyloP100: 0.470
Genes affected
PMS1 (HGNC:9121): (PMS1 homolog 1, mismatch repair system component) This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein. Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
Variant 2-189795957-G-A is Benign according to our data. Variant chr2-189795957-G-A is described in ClinVar as [Benign]. Clinvar id is 1274521.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMS1 | NM_000534.5 | c.315+6G>A | splice_donor_region_variant, intron_variant | ENST00000441310.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMS1 | ENST00000441310.7 | c.315+6G>A | splice_donor_region_variant, intron_variant | 1 | NM_000534.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0311 AC: 4727AN: 152130Hom.: 113 Cov.: 32
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GnomAD3 exomes AF: 0.0340 AC: 8538AN: 250968Hom.: 218 AF XY: 0.0326 AC XY: 4426AN XY: 135756
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GnomAD4 exome AF: 0.0357 AC: 50856AN: 1425850Hom.: 1123 Cov.: 25 AF XY: 0.0350 AC XY: 24893AN XY: 711716
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GnomAD4 genome ? AF: 0.0310 AC: 4724AN: 152248Hom.: 113 Cov.: 32 AF XY: 0.0322 AC XY: 2396AN XY: 74446
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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Name
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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