chr2-189818098-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000534.5(PMS1):āc.500A>Gā(p.Asp167Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,607,734 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_000534.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000328 AC: 50AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000477 AC: 119AN: 249506Hom.: 1 AF XY: 0.000519 AC XY: 70AN XY: 134934
GnomAD4 exome AF: 0.000186 AC: 270AN: 1455386Hom.: 3 Cov.: 27 AF XY: 0.000206 AC XY: 149AN XY: 724378
GnomAD4 genome AF: 0.000328 AC: 50AN: 152348Hom.: 0 Cov.: 32 AF XY: 0.000523 AC XY: 39AN XY: 74504
ClinVar
Submissions by phenotype
not provided Uncertain:1
The PMS1 p.Asp167Gly variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs200244068) and in control databases in 134 of 266706 chromosomes (1 homozygous) at a frequency of 0.0005024 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (Finnish) in 97 of 25048 chromosomes (freq: 0.003873), South Asian in 21 of 30364 chromosomes (freq: 0.000692), Other in 2 of 6660 chromosomes (freq: 0.0003), European (non-Finnish) in 13 of 117228 chromosomes (freq: 0.000111) and African in 1 of 23510 chromosomes (freq: 0.000043), but was not observed in the Latino, Ashkenazi Jewish, or East Asian populations. The p.Asp167 residue is not conserved in mammals and three of four computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM) suggest that the variant may impact the protein. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at