rs1063646

Variant names:

• chr6-31139871-C-T
• rs1063646
• NM_014068.3:c.398C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• 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
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PSORS1C1	NM_014068.3	c.398C>T	p.Pro133Leu	missense_variant	Exon 6 of 6	ENST00000259881.10	NP_054787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSORS1C1	ENST00000259881.10	c.398C>T	p.Pro133Leu	missense_variant	Exon 6 of 6	1	NM_014068.3	ENSP00000259881.9
PSORS1C1	ENST00000479581.5	n.292C>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
PSORS1C1	ENST00000547221.1	c.254C>T	p.Pro85Leu	missense_variant	Exon 4 of 4	3		ENSP00000449471.1
PSORS1C1	ENST00000481450.2	c.209C>T	p.Pro70Leu	missense_variant	Exon 2 of 2	2		ENSP00000447158.1

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

GnomAD2 exomes AF: 0.146 AC: 36074 AN: 246988 AF XY: 0.149

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 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

African (AFR) AF: 0.161 AC: 5403 AN: 33474

American (AMR) AF: 0.111 AC: 4951 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4058 AN: 26134

East Asian (EAS) AF: 0.114 AC: 4533 AN: 39700

South Asian (SAS) AF: 0.148 AC: 12724 AN: 86254

European-Finnish (FIN) AF: 0.117 AC: 6150 AN: 52362

Middle Eastern (MID) AF: 0.178 AC: 1029 AN: 5768

European-Non Finnish (NFE) AF: 0.171 AC: 189790 AN: 1111766

Other (OTH) AF: 0.159 AC: 9604 AN: 60382

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

African (AFR) AF: 0.161 AC: 6692 AN: 41474

American (AMR) AF: 0.142 AC: 2177 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3470

East Asian (EAS) AF: 0.107 AC: 553 AN: 5162

South Asian (SAS) AF: 0.145 AC: 701 AN: 4824

European-Finnish (FIN) AF: 0.116 AC: 1226 AN: 10606

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11226 AN: 67964

Other (OTH) AF: 0.173 AC: 365 AN: 2112

Alfa AF: 0.161 Hom.: 7142

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

Nov 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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;.;.
PhyloP100		-0.059
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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