6-31138722-G-A

Variant names:

• chr6-31138722-G-A
• rs9263726
• NM_014068.3:c.110G>A

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.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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). 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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.27
• Publications: 52 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=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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSORS1C1	NM_014068.3	MANE Select	c.110G>A	p.Arg37His	missense	Exon 5 of 6	NP_054787.2
	PSORS1C2	NM_014069.3	MANE Select	c.55+250C>T		intron	N/A	NP_054788.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.110G>A	p.Arg37His	missense	Exon 5 of 6	ENSP00000259881.9
	PSORS1C1	ENST00000552747.1	TSL:1	n.417G>A		non_coding_transcript_exon	Exon 2 of 2
	PSORS1C2	ENST00000259845.5	TSL:1 MANE Select	c.55+250C>T		intron	N/A	ENSP00000259845.4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 19928 AN: 146574 Hom.: 1406 Cov.: 30

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

GnomAD2 exomes AF: 0.115 AC: 27655 AN: 241276 AF XY: 0.114

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 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.: 52 AF XY: 0.124 AC XY: 89886 AN XY: 727122

African (AFR) AF: 0.168 AC: 5637 AN: 33476

American (AMR) AF: 0.0903 AC: 4036 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0829 AC: 2166 AN: 26128

East Asian (EAS) AF: 0.0466 AC: 1849 AN: 39700

South Asian (SAS) AF: 0.0737 AC: 6352 AN: 86242

European-Finnish (FIN) AF: 0.100 AC: 5333 AN: 53274

Middle Eastern (MID) AF: 0.129 AC: 742 AN: 5764

European-Non Finnish (NFE) AF: 0.134 AC: 149382 AN: 1111924

Other (OTH) AF: 0.122 AC: 7355 AN: 60386

GnomAD4 genome AF: 0.136 AC: 19962 AN: 146690 Hom.: 1412 Cov.: 30 AF XY: 0.134 AC XY: 9565 AN XY: 71480

African (AFR) AF: 0.170 AC: 6840 AN: 40140

American (AMR) AF: 0.124 AC: 1792 AN: 14430

Ashkenazi Jewish (ASJ) AF: 0.0935 AC: 286 AN: 3060

East Asian (EAS) AF: 0.0747 AC: 373 AN: 4990

South Asian (SAS) AF: 0.0703 AC: 315 AN: 4482

European-Finnish (FIN) AF: 0.104 AC: 1030 AN: 9880

Middle Eastern (MID) AF: 0.123 AC: 34 AN: 276

European-Non Finnish (NFE) AF: 0.133 AC: 8871 AN: 66558

Other (OTH) AF: 0.154 AC: 310 AN: 2010

Alfa AF: 0.128 Hom.: 5901

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.48
DANN	Benign	0.92
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0069	N
MetaRNN	Benign	0.00093	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-3.3
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.050
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.040
MPC		0.58
ClinPred		0.015	T
GERP RS		-4.9
PromoterAI		0.0082	Neutral
Varity_R		0.019
gMVP		0.011
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9263726; hg19: chr6-31106499; COSMIC: COSV52535056; COSMIC: COSV52535056;