6-31138712-G-A

Variant names:

• chr6-31138712-G-A
• rs1265096
• NM_014068.3:c.100G>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.100G>A​(p.Glu34Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 1,603,722 control chromosomes in the GnomAD database, including 3,521 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.048 (251 hom., cov: 31)
  • Exomes 𝑓: 0.059 (3270 hom.)
• Consequence: PSORS1C1 NM_014068.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.02
• Publications: 23 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=0.0018762052).
• BP6: Variant 6-31138712-G-A is Benign according to our data. Variant chr6-31138712-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056342.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 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.100G>A	p.Glu34Lys	missense	Exon 5 of 6	NP_054787.2
	PSORS1C2	NM_014069.3	MANE Select	c.55+260C>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.100G>A	p.Glu34Lys	missense	Exon 5 of 6	ENSP00000259881.9
	PSORS1C1	ENST00000552747.1	TSL:1	n.407G>A		non_coding_transcript_exon	Exon 2 of 2
	PSORS1C2	ENST00000259845.5	TSL:1 MANE Select	c.55+260C>T		intron	N/A	ENSP00000259845.4

Frequencies

GnomAD3 genomes AF: 0.0481 AC: 6828 AN: 141910 Hom.: 251 Cov.: 31

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.0489

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00766

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00513

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.00709

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0240

GnomAD2 exomes AF: 0.0467 AC: 11534 AN: 246924 AF XY: 0.0466

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.00734

Gnomad ASJ exome AF: 0.00432

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0742

Gnomad OTH exome AF: 0.0394

GnomAD4 exome AF: 0.0587 AC: 85875 AN: 1461708 Hom.: 3270 Cov.: 52 AF XY: 0.0570 AC XY: 41420 AN XY: 727160

African (AFR) AF: 0.00905 AC: 303 AN: 33480

American (AMR) AF: 0.00778 AC: 348 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00494 AC: 129 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00452 AC: 390 AN: 86258

European-Finnish (FIN) AF: 0.110 AC: 5853 AN: 53272

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.0686 AC: 76331 AN: 1111984

Other (OTH) AF: 0.0413 AC: 2497 AN: 60392

GnomAD4 genome AF: 0.0481 AC: 6827 AN: 142014 Hom.: 251 Cov.: 31 AF XY: 0.0476 AC XY: 3297 AN XY: 69256

African (AFR) AF: 0.0138 AC: 525 AN: 38164

American (AMR) AF: 0.0161 AC: 225 AN: 13978

Ashkenazi Jewish (ASJ) AF: 0.00766 AC: 23 AN: 3002

East Asian (EAS) AF: 0.000200 AC: 1 AN: 5012

South Asian (SAS) AF: 0.00492 AC: 22 AN: 4472

European-Finnish (FIN) AF: 0.117 AC: 1147 AN: 9778

Middle Eastern (MID) AF: 0.00763 AC: 2 AN: 262

European-Non Finnish (NFE) AF: 0.0742 AC: 4796 AN: 64614

Other (OTH) AF: 0.0238 AC: 45 AN: 1894

Alfa AF: 0.0540 Hom.: 943

Bravo AF: 0.0365

TwinsUK AF: 0.0787 AC: 292

ALSPAC AF: 0.0729 AC: 281

ESP6500AA AF: 0.0165 AC: 50

ESP6500EA AF: 0.0666 AC: 361

ExAC AF: 0.0507 AC: 6108

Asia WGS AF: 0.00404 AC: 15 AN: 3478

EpiCase AF: 0.0528

EpiControl AF: 0.0521

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PSORS1C1-related disorder Benign:1

Oct 21, 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	0.15
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.97
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Benign	0.33	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.84	P
Vest4		0.054
MPC		0.84
ClinPred		0.0052	T
GERP RS		0.35
PromoterAI		-0.0039	Neutral
Varity_R		0.022
gMVP		0.072
Mutation Taster		=99/1	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: rs1265096; hg19: chr6-31106489; COSMIC: COSV52536827; COSMIC: COSV52536827;