rs2233952

Variant names:

• chr6-31138114-A-G
• rs2233952
• NM_014069.3:c.248T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31138114-A-G
• chr6-31138114-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014069.3(PSORS1C2):​c.248T>C​(p.Leu83Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 1,603,552 control chromosomes in the GnomAD database, including 635,038 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.92 (64250 hom., cov: 29)
  • Exomes 𝑓: 0.89 (570788 hom.)
• Consequence: PSORS1C2 NM_014069.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

Genes affected

PSORS1C2 (HGNC:17199): (psoriasis susceptibility 1 candidate 2) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1602834E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C2	NM_014069.3	c.248T>C	p.Leu83Pro	missense_variant	Exon 2 of 2	ENST00000259845.5	NP_054788.2
PSORS1C1	NM_014068.3	c.14-316A>G		intron_variant	Intron 3 of 5	ENST00000259881.10	NP_054787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSORS1C2	ENST00000259845.5	c.248T>C	p.Leu83Pro	missense_variant	Exon 2 of 2	1	NM_014069.3	ENSP00000259845.4
PSORS1C1	ENST00000259881.10	c.14-316A>G		intron_variant	Intron 3 of 5	1	NM_014068.3	ENSP00000259881.9

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139496 AN: 151896 Hom.: 64187 Cov.: 29

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.938

GnomAD3 exomes AF: 0.903 AC: 213828 AN: 236744 Hom.: 96805 AF XY: 0.904 AC XY: 117075 AN XY: 129532

Gnomad AFR exome AF: 0.979

Gnomad AMR exome AF: 0.906

Gnomad ASJ exome AF: 0.979

Gnomad EAS exome AF: 0.942

Gnomad SAS exome AF: 0.921

Gnomad FIN exome AF: 0.864

Gnomad NFE exome AF: 0.882

Gnomad OTH exome AF: 0.901

GnomAD4 exome AF: 0.886 AC: 1286203 AN: 1451538 Hom.: 570788 Cov.: 47 AF XY: 0.888 AC XY: 640765 AN XY: 721780

Gnomad4 AFR exome AF: 0.982

Gnomad4 AMR exome AF: 0.906

Gnomad4 ASJ exome AF: 0.979

Gnomad4 EAS exome AF: 0.944

Gnomad4 SAS exome AF: 0.922

Gnomad4 FIN exome AF: 0.866

Gnomad4 NFE exome AF: 0.875

Gnomad4 OTH exome AF: 0.901

GnomAD4 genome AF: 0.918 AC: 139621 AN: 152014 Hom.: 64250 Cov.: 29 AF XY: 0.918 AC XY: 68220 AN XY: 74276

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.938

Alfa AF: 0.893 Hom.: 98020

Bravo AF: 0.925

TwinsUK AF: 0.879 AC: 3258

ALSPAC AF: 0.878 AC: 3384

ESP6500AA AF: 0.971 AC: 2862

ESP6500EA AF: 0.886 AC: 4755

ExAC AF: 0.904 AC: 105242

Asia WGS AF: 0.932 AC: 3242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.029
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	20
DANN	Benign	0.77
DEOGEN2	Benign	0.00087	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-2.0	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	4.0	N
REVEL	Benign	0.076
Sift	Benign	1.0	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.071
MPC		0.53
ClinPred		0.0022	T
GERP RS		4.7
Varity_R		0.079
gMVP		0.032

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

Publications

LitVar

Other links and lift over

dbSNP: rs2233952; hg19: chr6-31105891; COSMIC: COSV52535359; COSMIC: COSV52535359;