Genetic Variant PSORS1C1:p.Arg37Cys (chr6-31138721-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014068.3(PSORS1C1):c.109C>T(p.Arg37Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,590,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PSORS1C1
NM_014068.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0270

Publications

0 publications found

Variant links:

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]

PSORS1C1 links:

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

PSORS1C2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.025246501).

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>T	p.Arg37Cys	missense	Exon 5 of 6	NP_054787.2	Q9UIG5-1
	PSORS1C2	NM_014069.3	MANE Select	c.55+251G>A		intron	N/A	NP_054788.2	Q9UIG4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.109C>T	p.Arg37Cys	missense	Exon 5 of 6	ENSP00000259881.9	Q9UIG5-1
PSORS1C2	ENST00000259845.5	TSL:1 MANE Select	c.55+251G>A		intron	N/A	ENSP00000259845.4	Q9UIG4
PSORS1C1	ENST00000552747.1	TSL:1	n.416C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000145

AC:

AN:

137508

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000149

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000217

AC:

AN:

230120

AF XY:

0.00000800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1452640

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

723164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33216

American (AMR)

AF:

0.0000224

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39676

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

1103690

Other (OTH)

AF:

0.00

AC:

AN:

60112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000145

AC:

AN:

137614

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

66992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36788

American (AMR)

AF:

0.000149

AC:

AN:

13404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2850

East Asian (EAS)

AF:

0.00

AC:

AN:

4910

South Asian (SAS)

AF:

0.00

AC:

AN:

4330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62976

Other (OTH)

AF:

0.00

AC:

AN:

1838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000254

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.1

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0090

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00032

M_CAP

Benign

0.0025

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

0.027

PrimateAI

Benign

0.21

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.034

Sift

Pathogenic

0.0

Polyphen

0.0050

Vest4

0.17

MutPred

0.20

Loss of disorder (P = 0.1081)

MVP

0.095

MPC

0.55

ClinPred

0.090

GERP RS

-0.53

PromoterAI

-0.022

Neutral

(source)

Varity_R

0.065

gMVP

0.0097

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over