rs540640358

Variant names:

• chr6-31138721-C-G
• rs540640358
• NM_014068.3:c.109C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-31138721-C-G
• chr6-31138721-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014068.3(PSORS1C1):​c.109C>G​(p.Arg37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R37H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PSORS1C1 NM_014068.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04647392).

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.109C>G	p.Arg37Gly	missense	Exon 5 of 6	NP_054787.2	Q9UIG5-1
	PSORS1C2	NM_014069.3	MANE Select	c.55+251G>C		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.109C>G	p.Arg37Gly	missense	Exon 5 of 6	ENSP00000259881.9	Q9UIG5-1
	PSORS1C2	ENST00000259845.5	TSL:1 MANE Select	c.55+251G>C		intron	N/A	ENSP00000259845.4	Q9UIG4
	PSORS1C1	ENST00000552747.1	TSL:1	n.416C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000435 AC: 1 AN: 230120 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000121

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452640 Hom.: 0 Cov.: 47 AF XY: 0.00000138 AC XY: 1 AN XY: 723164

African (AFR) AF: 0.00 AC: 0 AN: 33216

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103690

Other (OTH) AF: 0.00 AC: 0 AN: 60112

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.075
DANN	Benign	0.93
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.027
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.034
Sift	Pathogenic	0.0	D
Polyphen		0.027	B
Vest4		0.14
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.12
MPC		0.53
ClinPred		0.063	T
GERP RS		-0.53
PromoterAI		-0.035	Neutral
Varity_R		0.070
gMVP		0.012
Mutation Taster		=100/0	polymorphism

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: rs540640358; hg19: chr6-31106498;