Variant 6-31138739-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_014068.3(PSORS1C1):c.127C>T(p.Pro43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,613,950 control chromosomes in the GnomAD database, including 2,128 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.063 ( 498 hom., cov: 31)

Exomes 𝑓: 0.033 ( 1630 hom. )

Consequence

PSORS1C1
NM_014068.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.277

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011078715).

BP6

Variant 6-31138739-C-T is Benign according to our data. Variant chr6-31138739-C-T is described in ClinVar as [Benign]. Clinvar id is 3059976.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSORS1C1	NM_014068.3 linkuse as main transcript	c.127C>T	p.Pro43Ser	missense_variant	5/6	ENST00000259881.10
PSORS1C2	NM_014069.3 linkuse as main transcript	c.55+233G>A		intron_variant		ENST00000259845.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSORS1C1	ENST00000259881.10 linkuse as main transcript	c.127C>T	p.Pro43Ser	missense_variant	5/6	1	NM_014068.3	P2	Q9UIG5-1
PSORS1C2	ENST00000259845.5 linkuse as main transcript	c.55+233G>A		intron_variant		1	NM_014069.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9619

AN:

151996

Hom.:

496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0342

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.0415

Gnomad FIN

AF:

0.0529

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0241

Gnomad OTH

AF:

0.0623

GnomAD3 exomes

AF:

0.0462

AC:

11487

AN:

248662

Hom.:

541

AF XY:

0.0441

AC XY:

5947

AN XY:

134896

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.0224

Gnomad ASJ exome

AF:

0.0315

Gnomad EAS exome

AF:

0.162

Gnomad SAS exome

AF:

0.0378

Gnomad FIN exome

AF:

0.0561

Gnomad NFE exome

AF:

0.0236

Gnomad OTH exome

AF:

0.0418

GnomAD4 exome

AF:

0.0334

AC:

48847

AN:

1461838

Hom.:

1630

Cov.:

AF XY:

0.0331

AC XY:

24043

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0247

Gnomad4 ASJ exome

AF:

0.0287

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.0362

Gnomad4 FIN exome

AF:

0.0578

Gnomad4 NFE exome

AF:

0.0234

Gnomad4 OTH exome

AF:

0.0467

GnomAD4 genome

AF:

0.0633

AC:

9623

AN:

152112

Hom.:

498

Cov.:

AF XY:

0.0643

AC XY:

4784

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.0265

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.0415

Gnomad4 FIN

AF:

0.0529

Gnomad4 NFE

AF:

0.0241

Gnomad4 OTH

AF:

0.0631

Alfa

AF:

0.0340

Hom.:

335

Bravo

AF:

0.0669

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0228

AC:

ESP6500AA

AF:

0.129

AC:

390

ESP6500EA

AF:

0.0233

AC:

126

ExAC

AF:

0.0470

AC:

5704

Asia WGS

AF:

0.112

AC:

389

AN:

3478

EpiCase

AF:

0.0208

EpiControl

AF:

0.0238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PSORS1C1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.9

DANN

Benign

0.96

DEOGEN2

Benign

0.0088

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00044

MetaRNN

Benign

0.0011

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.094

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0060

Vest4

0.033

MPC

0.42

ClinPred

0.026

GERP RS

-2.5

Varity_R

0.024

gMVP

0.034

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over