6-31138728-C-A

Variant names:

• chr6-31138728-C-A
• NM_014068.3:c.116C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014068.3(PSORS1C1):​c.116C>A​(p.Pro39His) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSORS1C1 NM_014068.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076485515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSORS1C1	NM_014068.3	c.116C>A	p.Pro39His	missense_variant	Exon 5 of 6	ENST00000259881.10	NP_054787.2
PSORS1C2	NM_014069.3	c.55+244G>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.116C>A	p.Pro39His	missense_variant	Exon 5 of 6	1	NM_014068.3	ENSP00000259881.9
PSORS1C2	ENST00000259845.5	c.55+244G>T		intron_variant	Intron 1 of 1	1	NM_014069.3	ENSP00000259845.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.020	N
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.034
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.69	P
Vest4		0.13
MutPred		0.20		Loss of catalytic residue at P38 (P = 0.0191);
MVP		0.20
MPC		1.3
ClinPred		0.21	T
GERP RS		-1.4
Varity_R		0.037
gMVP		0.024

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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: chr6-31106505;