6-31138739-C-T

Variant names:

• chr6-31138739-C-T
• rs9501057
• NM_014068.3:c.127C>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.127C>T​(p.Pro43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,613,950 control chromosomes in the GnomAD database, including 2,128 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 0.063 (498 hom., cov: 31)
  • Exomes 𝑓: 0.033 (1630 hom.)
• Consequence: PSORS1C1 NM_014068.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.277
• Publications: 15 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]

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011078715).
• BP6: Variant 6-31138739-C-T is Benign according to our data. Variant chr6-31138739-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059976.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014068.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSORS1C1	NM_014068.3	MANE Select	c.127C>T	p.Pro43Ser	missense	Exon 5 of 6	NP_054787.2
	PSORS1C2	NM_014069.3	MANE Select	c.55+233G>A		intron	N/A	NP_054788.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.127C>T	p.Pro43Ser	missense	Exon 5 of 6	ENSP00000259881.9
	PSORS1C2	ENST00000259845.5	TSL:1 MANE Select	c.55+233G>A		intron	N/A	ENSP00000259845.4
	PSORS1C1	ENST00000552747.1	TSL:1	n.434C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9619 AN: 151996 Hom.: 496 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0529

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0623

GnomAD2 exomes AF: 0.0462 AC: 11487 AN: 248662 AF XY: 0.0441

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.0224

Gnomad ASJ exome AF: 0.0315

Gnomad EAS exome AF: 0.162

Gnomad FIN exome AF: 0.0561

Gnomad NFE exome AF: 0.0236

Gnomad OTH exome AF: 0.0418

GnomAD4 exome AF: 0.0334 AC: 48847 AN: 1461838 Hom.: 1630 Cov.: 38 AF XY: 0.0331 AC XY: 24043 AN XY: 727222

African (AFR) AF: 0.139 AC: 4647 AN: 33478

American (AMR) AF: 0.0247 AC: 1106 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0287 AC: 751 AN: 26134

East Asian (EAS) AF: 0.178 AC: 7063 AN: 39698

South Asian (SAS) AF: 0.0362 AC: 3125 AN: 86258

European-Finnish (FIN) AF: 0.0578 AC: 3089 AN: 53398

Middle Eastern (MID) AF: 0.0319 AC: 184 AN: 5768

European-Non Finnish (NFE) AF: 0.0234 AC: 26059 AN: 1111988

Other (OTH) AF: 0.0467 AC: 2823 AN: 60394

GnomAD4 genome AF: 0.0633 AC: 9623 AN: 152112 Hom.: 498 Cov.: 31 AF XY: 0.0643 AC XY: 4784 AN XY: 74364

African (AFR) AF: 0.136 AC: 5640 AN: 41468

American (AMR) AF: 0.0342 AC: 522 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3466

East Asian (EAS) AF: 0.157 AC: 810 AN: 5160

South Asian (SAS) AF: 0.0415 AC: 200 AN: 4814

European-Finnish (FIN) AF: 0.0529 AC: 560 AN: 10594

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0241 AC: 1641 AN: 68016

Other (OTH) AF: 0.0631 AC: 133 AN: 2108

Alfa AF: 0.0370 Hom.: 580

Bravo AF: 0.0669

TwinsUK AF: 0.0227 AC: 84

ALSPAC AF: 0.0228 AC: 88

ESP6500AA AF: 0.129 AC: 390

ESP6500EA AF: 0.0233 AC: 126

ExAC AF: 0.0470 AC: 5704

Asia WGS AF: 0.112 AC: 389 AN: 3478

EpiCase AF: 0.0208

EpiControl AF: 0.0238

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PSORS1C1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.96
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00044	N
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.28
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.094
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0060	B
Vest4		0.033
MPC		0.42
ClinPred		0.026	T
GERP RS		-2.5
PromoterAI		-0.0030	Neutral
Varity_R		0.024
gMVP		0.034
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs9501057; hg19: chr6-31106516; COSMIC: COSV52535905; COSMIC: COSV52535905;