rs5741593

chr2-189824998-A-AT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000534.5(PMS1):c.582+6821dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 152,118 control chromosomes in the GnomAD database, including 847 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.097 (847 hom., cov: 31)
• Consequence: PMS1 NM_000534.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5	c.582+6821dup		intron_variant		ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7	c.582+6821dup		intron_variant		1	NM_000534.5	P1

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14800 AN: 152000 Hom.: 851 Cov.: 31

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0547

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.0908

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0973 AC: 14799 AN: 152118 Hom.: 847 Cov.: 31 AF XY: 0.0985 AC XY: 7325 AN XY: 74370

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0546

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0663

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0825 Hom.: 80

Bravo AF: 0.0959

Asia WGS AF: 0.0880 AC: 306 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs5741593; hg19: chr2-190689724;