Variant 6-31138722-G-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.110G>A(p.Arg37His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,608,304 control chromosomes in the GnomAD database, including 13,529 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.14 ( 1412 hom., cov: 30)

Exomes 𝑓: 0.13 ( 12117 hom. )

Consequence

PSORS1C1
NM_014068.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.27

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=9.252429E-4).

BP6

Variant 6-31138722-G-A is Benign according to our data. Variant chr6-31138722-G-A is described in ClinVar as [Benign]. Clinvar id is 3059106.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 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.110G>A	p.Arg37His	missense_variant	5/6	ENST00000259881.10
PSORS1C2	NM_014069.3 linkuse as main transcript	c.55+250C>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.110G>A	p.Arg37His	missense_variant	5/6	1	NM_014068.3	P2	Q9UIG5-1
PSORS1C2	ENST00000259845.5 linkuse as main transcript	c.55+250C>T		intron_variant		1	NM_014069.3	P1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

19928

AN:

146574

Hom.:

1406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0935

Gnomad EAS

AF:

0.0746

Gnomad SAS

AF:

0.0689

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.122

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.115

AC:

27655

AN:

241276

Hom.:

1745

AF XY:

0.114

AC XY:

14990

AN XY:

131098

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.0873

Gnomad ASJ exome

AF:

0.0908

Gnomad EAS exome

AF:

0.0986

Gnomad SAS exome

AF:

0.0723

Gnomad FIN exome

AF:

0.0994

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.125

AC:

182852

AN:

1461614

Hom.:

12117

Cov.:

AF XY:

0.124

AC XY:

89886

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0903

Gnomad4 ASJ exome

AF:

0.0829

Gnomad4 EAS exome

AF:

0.0466

Gnomad4 SAS exome

AF:

0.0737

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.136

AC:

19962

AN:

146690

Hom.:

1412

Cov.:

AF XY:

0.134

AC XY:

9565

AN XY:

71480

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.0935

Gnomad4 EAS

AF:

0.0747

Gnomad4 SAS

AF:

0.0703

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.129

Hom.:

2896

Bravo

AF:

0.136

TwinsUK

AF:

0.126

AC:

468

ALSPAC

AF:

0.141

AC:

545

ExAC

AF:

0.115

AC:

13808

Asia WGS

AF:

0.100

AC:

346

AN:

3460

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 08, 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

0.066

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.48

DANN

Benign

0.92

DEOGEN2

Benign

0.010

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0069

MetaRNN

Benign

0.00093

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.050

Sift

Pathogenic

0.0

Polyphen

0.0

Vest4

0.040

MPC

0.58

ClinPred

0.015

GERP RS

-4.9

Varity_R

0.019

gMVP

0.011

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