Variant 6-31138682-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_014068.3(PSORS1C1):c.70C>A(p.Pro24Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,958 control chromosomes in the GnomAD database, including 9,966 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1232 hom., cov: 30)

Exomes 𝑓: 0.10 ( 8734 hom. )

Consequence

PSORS1C1
NM_014068.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.714

Variant links:

Genes affected

PSORS1C1 (HGNC:17202): (psoriasis susceptibility 1 candidate 1) This gene is one of several genes thought to confer susceptibility to psoriasis and systemic sclerosis, located on chromosome 6 near the major histocompatibility complex (MHC) class I region. [provided by RefSeq, Sep 2011]

PSORS1C1 links:

PSORS1C2 (HGNC:17199): (psoriasis susceptibility 1 candidate 2) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PSORS1C2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052095354).

BP6

Variant 6-31138682-C-A is Benign according to our data. Variant chr6-31138682-C-A is described in ClinVar as [Benign]. Clinvar id is 3059991.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSORS1C1	NM_014068.3 linkuse as main transcript	c.70C>A	p.Pro24Thr	missense_variant	5/6	ENST00000259881.10
PSORS1C2	NM_014069.3 linkuse as main transcript	c.55+290G>T		intron_variant		ENST00000259845.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSORS1C1	ENST00000259881.10 linkuse as main transcript	c.70C>A	p.Pro24Thr	missense_variant	5/6	1	NM_014068.3	P2	Q9UIG5-1
PSORS1C2	ENST00000259845.5 linkuse as main transcript	c.55+290G>T		intron_variant		1	NM_014069.3	P1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18385

AN:

151702

Hom.:

1231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.0427

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.130

AC:

31989

AN:

246934

Hom.:

2457

AF XY:

0.128

AC XY:

17175

AN XY:

134446

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.0457

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.100

AC:

146719

AN:

1461138

Hom.:

8734

Cov.:

AF XY:

0.101

AC XY:

73541

AN XY:

726876

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.0462

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.0888

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.121

AC:

18403

AN:

151820

Hom.:

1232

Cov.:

AF XY:

0.124

AC XY:

9209

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.0428

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.119

Hom.:

582

Bravo

AF:

0.123

TwinsUK

AF:

0.0801

AC:

297

ALSPAC

AF:

0.0854

AC:

329

ESP6500AA

AF:

0.120

AC:

362

ESP6500EA

AF:

0.112

AC:

609

ExAC

AF:

0.122

AC:

14632

Asia WGS

AF:

0.0850

AC:

298

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.131

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PSORS1C1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.1

DANN

Benign

0.97

DEOGEN2

Benign

0.0094

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.059

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.22

Vest4

0.20

MPC

1.1

ClinPred

0.033

GERP RS

-0.43

Varity_R

0.057

gMVP

0.021

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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