Variant 2-189784590-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000534.5(PMS1):c.-24G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 153,002 control chromosomes in the GnomAD database, including 4,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4226 hom., cov: 33)

Exomes 𝑓: 0.18 ( 11 hom. )

Consequence

PMS1
NM_000534.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.285

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 2-189784590-G-C is Benign according to our data. Variant chr2-189784590-G-C is described in ClinVar as [Benign]. Clinvar id is 1292222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5 linkuse as main transcript	c.-24G>C		5_prime_UTR_variant	1/13	ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7 linkuse as main transcript	c.-24G>C		5_prime_UTR_variant	1/13	1	NM_000534.5	P1	P54277-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34723

AN:

152102

Hom.:

4218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.219

GnomAD4 exome

AF:

0.179

AC:

140

AN:

782

Hom.:

Cov.:

AF XY:

0.162

AC XY:

AN XY:

426

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.0882

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.228

AC:

34750

AN:

152220

Hom.:

4226

Cov.:

AF XY:

0.226

AC XY:

16796

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.252

Gnomad4 ASJ

AF:

0.213

Gnomad4 EAS

AF:

0.226

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.194

Gnomad4 NFE

AF:

0.197

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.134

Hom.:

254

Bravo

AF:

0.236

Asia WGS

AF:

0.201

AC:

699

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over