Variant 6-31138746-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014068.3(PSORS1C1):c.134G>A(p.Arg45Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00074 in 1,613,990 control chromosomes in the GnomAD database, including 11 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 (★).

Frequency

Genomes: 𝑓 0.0038 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 4 hom. )

Consequence

PSORS1C1
NM_014068.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.50

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:

PSORS1C1 (HGNC:):

PSORS1C1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028287172).

BP6

Variant 6-31138746-G-A is Benign according to our data. Variant chr6-31138746-G-A is described in ClinVar as [Benign]. Clinvar id is 784067.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSORS1C1	NM_014068.3 linkuse as main transcript	c.134G>A	p.Arg45Gln	missense_variant	5/6	ENST00000259881.10	NP_054787.2	Q9UIG5-1D2IYL0
PSORS1C2	NM_014069.3 linkuse as main transcript	c.55+226C>T		intron_variant		ENST00000259845.5	NP_054788.2	Q9UIG4A0A1U9X9A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSORS1C1	ENST00000259881.10 linkuse as main transcript	c.134G>A	p.Arg45Gln	missense_variant	5/6	1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1
PSORS1C2	ENST00000259845.5 linkuse as main transcript	c.55+226C>T		intron_variant		1	NM_014069.3	ENSP00000259845.4		Q9UIG4

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

560

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000911

AC:

227

AN:

249046

Hom.:

AF XY:

0.000630

AC XY:

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.0128

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000446

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000427

AC:

624

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000367

AC XY:

267

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00375

AC:

571

AN:

152134

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

289

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000202

Hom.:

Bravo

AF:

0.00426

ESP6500AA

AF:

0.0149

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00117

AC:

142

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PSORS1C1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2020

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.041

DANN

Benign

0.85

DEOGEN2

Benign

0.014

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.021

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.017

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0090

Vest4

0.13

MVP

0.040

MPC

0.47

ClinPred

0.014

GERP RS

-6.0

Varity_R

0.022

gMVP

0.012

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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