rs1063646

Positions:

• chr6-31139871-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_014068.3(PSORS1C1):​c.398C>T​(p.Pro133Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,612,660 control chromosomes in the GnomAD database, including 21,932 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 0.16 (1931 hom., cov: 31)
  • Exomes 𝑓: 0.16 (20001 hom.)
• Consequence: PSORS1C1 NM_014068.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0590

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015360415).
• BP6: Variant 6-31139871-C-T is Benign according to our data. Variant chr6-31139871-C-T is described in ClinVar as [Benign]. Clinvar id is 3059182.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSORS1C1	NM_014068.3	c.398C>T	p.Pro133Leu	missense_variant	6/6	ENST00000259881.10	NP_054787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSORS1C1	ENST00000259881.10	c.398C>T	p.Pro133Leu	missense_variant	6/6	1	NM_014068.3	ENSP00000259881	P2
PSORS1C1	ENST00000479581.5	n.292C>T		non_coding_transcript_exon_variant	2/2	1
PSORS1C1	ENST00000547221.1	c.254C>T	p.Pro85Leu	missense_variant	4/4	3		ENSP00000449471	A2
PSORS1C1	ENST00000481450.2	c.209C>T	p.Pro70Leu	missense_variant	2/2	2		ENSP00000447158

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23577 AN: 151978 Hom.: 1922 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.176

GnomAD3 exomes AF: 0.146 AC: 36074 AN: 246988 Hom.: 2876 AF XY: 0.149 AC XY: 20076 AN XY: 134576

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.110

Gnomad SAS exome AF: 0.146

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.163 AC: 238242 AN: 1460564 Hom.: 20001 Cov.: 34 AF XY: 0.163 AC XY: 118443 AN XY: 726630

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.155 AC: 23624 AN: 152096 Hom.: 1931 Cov.: 31 AF XY: 0.153 AC XY: 11412 AN XY: 74356

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.173

Alfa AF: 0.162 Hom.: 3262

Bravo AF: 0.155

TwinsUK AF: 0.162 AC: 599

ALSPAC AF: 0.181 AC: 696

ESP6500AA AF: 0.172 AC: 519

ESP6500EA AF: 0.166 AC: 899

ExAC AF: 0.149 AC: 17683

Asia WGS AF: 0.134 AC: 466 AN: 3478

EpiCase AF: 0.175

EpiControl AF: 0.181

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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	0.27
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.013	T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.46	.;T;T
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-7.6	D;D;D
REVEL	Benign	0.086
Sift	Benign	0.93	T;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.23	B;.;.
Vest4		0.074
MPC		1.1
ClinPred		0.024	T
GERP RS		-0.12
Varity_R		0.037
gMVP		0.029

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: rs1063646; hg19: chr6-31107648; COSMIC: COSV52535812; COSMIC: COSV52535812;