rs9501057

Variant names:

• chr6-31138739-C-A
• NM_014068.3:c.127C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31138739-C-A
• chr6-31138739-C-G
• chr6-31138739-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014068.3(PSORS1C1):​c.127C>A​(p.Pro43Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P43S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PSORS1C1 NM_014068.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C1	NM_014068.3	c.127C>A	p.Pro43Thr	missense_variant	Exon 5 of 6	ENST00000259881.10	NP_054787.2
PSORS1C2	NM_014069.3	c.55+233G>T		intron_variant	Intron 1 of 1	ENST00000259845.5	NP_054788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSORS1C1	ENST00000259881.10	c.127C>A	p.Pro43Thr	missense_variant	Exon 5 of 6	1	NM_014068.3	ENSP00000259881.9
PSORS1C2	ENST00000259845.5	c.55+233G>T		intron_variant	Intron 1 of 1	1	NM_014069.3	ENSP00000259845.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.0
DANN	Benign	0.96
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.020	N
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.028
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.018	B
Vest4		0.095
MutPred		0.29		Gain of glycosylation at P43 (P = 0.0413);
MVP		0.055
MPC		0.46
ClinPred		0.10	T
GERP RS		-2.5
Varity_R		0.029
gMVP		0.027

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.44		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31106516;