Genetic Variant PMS1:c.*212A>G (chr2-189877648-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000534.5(PMS1):c.*212A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 512,102 control chromosomes in the GnomAD database, including 18,205 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 0.30 ( 11401 hom., cov: 32)

Exomes 𝑓: 0.16 ( 6804 hom. )

Consequence

PMS1
NM_000534.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.860

Variant links:

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]

PMS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMS1	NM_000534.5 link	c.*212A>G		downstream_gene_variant		ENST00000441310.7	NP_000525.1	P54277-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMS1	ENST00000441310.7 link	c.*212A>G		downstream_gene_variant		1	NM_000534.5	ENSP00000406490.3		P54277-1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44837

AN:

152000

Hom.:

11374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.693

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.159

AC:

57110

AN:

359986

Hom.:

6804

Cov.:

AF XY:

0.156

AC XY:

29179

AN XY:

187054

show subpopulations

Gnomad4 AFR exome

AF:

0.692

Gnomad4 AMR exome

AF:

0.209

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.295

AC:

44907

AN:

152116

Hom.:

11401

Cov.:

AF XY:

0.293

AC XY:

21774

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.693

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.173

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.254

Alfa

AF:

0.269

Hom.:

1834

Bravo

AF:

0.316

Asia WGS

AF:

0.214

AC:

743

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.31

DANN

Benign

0.55

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over