rs1265097

Variant names:

• chr6-31138682-C-A
• rs1265097
• NM_014068.3:c.70C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31138682-C-A
• chr6-31138682-C-G
• chr6-31138682-C-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.70C>A​(p.Pro24Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,958 control chromosomes in the GnomAD database, including 9,966 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 0.12 (1232 hom., cov: 30)
  • Exomes 𝑓: 0.10 (8734 hom.)
• Consequence: PSORS1C1 NM_014068.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.714
• Publications: 51 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=0.0052095354).
• BP6: Variant 6-31138682-C-A is Benign according to our data. Variant chr6-31138682-C-A is described in ClinVar as Benign. ClinVar VariationId is 3059991.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.165 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.70C>A	p.Pro24Thr	missense	Exon 5 of 6	NP_054787.2	Q9UIG5-1
	PSORS1C2	NM_014069.3	MANE Select	c.55+290G>T		intron	N/A	NP_054788.2	Q9UIG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.70C>A	p.Pro24Thr	missense	Exon 5 of 6	ENSP00000259881.9	Q9UIG5-1
	PSORS1C2	ENST00000259845.5	TSL:1 MANE Select	c.55+290G>T		intron	N/A	ENSP00000259845.4	Q9UIG4
	PSORS1C1	ENST00000552747.1	TSL:1	n.377C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18385 AN: 151702 Hom.: 1231 Cov.: 30

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.130 AC: 31989 AN: 246934 AF XY: 0.128

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.0457

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.100 AC: 146719 AN: 1461138 Hom.: 8734 Cov.: 54 AF XY: 0.101 AC XY: 73541 AN XY: 726876

African (AFR) AF: 0.120 AC: 4015 AN: 33476

American (AMR) AF: 0.204 AC: 9105 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6709 AN: 26132

East Asian (EAS) AF: 0.0462 AC: 1836 AN: 39700

South Asian (SAS) AF: 0.111 AC: 9562 AN: 86254

European-Finnish (FIN) AF: 0.165 AC: 8757 AN: 52924

Middle Eastern (MID) AF: 0.172 AC: 991 AN: 5768

European-Non Finnish (NFE) AF: 0.0888 AC: 98740 AN: 1111780

Other (OTH) AF: 0.116 AC: 7004 AN: 60384

GnomAD4 genome AF: 0.121 AC: 18403 AN: 151820 Hom.: 1232 Cov.: 30 AF XY: 0.124 AC XY: 9209 AN XY: 74180

African (AFR) AF: 0.116 AC: 4806 AN: 41390

American (AMR) AF: 0.171 AC: 2602 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3468

East Asian (EAS) AF: 0.0428 AC: 220 AN: 5138

South Asian (SAS) AF: 0.106 AC: 507 AN: 4802

European-Finnish (FIN) AF: 0.178 AC: 1877 AN: 10530

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6964 AN: 67944

Other (OTH) AF: 0.163 AC: 342 AN: 2104

Alfa AF: 0.110 Hom.: 2143

Bravo AF: 0.123

TwinsUK AF: 0.0801 AC: 297

ALSPAC AF: 0.0854 AC: 329

ESP6500AA AF: 0.120 AC: 362

ESP6500EA AF: 0.112 AC: 609

ExAC AF: 0.122 AC: 14632

Asia WGS AF: 0.0850 AC: 298 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.131

ClinVar

ClinVar submissions

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	0.13
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.97
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.033	N
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.71
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.059
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.22	B
Vest4		0.20
MPC		1.1
ClinPred		0.033	T
GERP RS		-0.43
PromoterAI		-0.0056	Neutral
Varity_R		0.057
gMVP		0.021
Mutation Taster		=300/0	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: rs1265097; hg19: chr6-31106459; COSMIC: COSV52535535; COSMIC: COSV52535535;