rs5742938

Positions:

• chr2-189785232-G-A
• chr2-189785232-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000534.5(PMS1):​c.-21+639G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,088 control chromosomes in the GnomAD database, including 29,931 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 0.59 (29931 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PMS1 NM_000534.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5	c.-21+639G>A		intron_variant		ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7	c.-21+639G>A		intron_variant		1	NM_000534.5	P1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89607 AN: 151968 Hom.: 29912 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.589 AC: 89639 AN: 152086 Hom.: 29931 Cov.: 33 AF XY: 0.593 AC XY: 44060 AN XY: 74336

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.621

Alfa AF: 0.686 Hom.: 12464

Bravo AF: 0.574

Asia WGS AF: 0.668 AC: 2323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5742938; hg19: chr2-190649958;