rs1265097

chr6-31138682-C-Achr6-31138682-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★). 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.714

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]

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

ACMG classification

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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	c.70C>A	p.Pro24Thr	missense_variant	5/6	ENST00000259881.10
PSORS1C2	NM_014069.3	c.55+290G>T		intron_variant		ENST00000259845.5

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18385 AN: 151702 Hom.: 1231 Cov.: 30

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

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.: 54 AF XY: 0.101 AC XY: 73541 AN XY: 726876

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.: 30 AF XY: 0.124 AC XY: 9209 AN XY: 74180

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: criteria provided, single submitter

Submissions by phenotype

PSORS1C1-related disorder Benign:1

Benign, criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.1
Dann	Benign	0.97
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.033	N
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.059
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.22	B
Vest4		0.20
MPC		1.1
ClinPred		0.033	T
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

Other links and lift over

dbSNP: rs1265097; hg19: chr6-31106459; COSMIC: COSV52535535; COSMIC: COSV52535535;