Variant 6-31138712-G-A 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.100G>A(p.Glu34Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 1,603,722 control chromosomes in the GnomAD database, including 3,521 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E34Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.048 ( 251 hom., cov: 31)

Exomes 𝑓: 0.059 ( 3270 hom. )

Consequence

PSORS1C1
NM_014068.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.02

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=0.0018762052).

BP6

Variant 6-31138712-G-A is Benign according to our data. Variant chr6-31138712-G-A is described in ClinVar as [Benign]. Clinvar id is 3056342.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 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.100G>A	p.Glu34Lys	missense_variant	5/6	ENST00000259881.10
PSORS1C2	NM_014069.3 linkuse as main transcript	c.55+260C>T		intron_variant		ENST00000259845.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSORS1C1	ENST00000259881.10 linkuse as main transcript	c.100G>A	p.Glu34Lys	missense_variant	5/6	1	NM_014068.3	P2	Q9UIG5-1
PSORS1C2	ENST00000259845.5 linkuse as main transcript	c.55+260C>T		intron_variant		1	NM_014069.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0481

AC:

6828

AN:

141910

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.0489

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.00766

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.00513

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.00709

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.0240

GnomAD3 exomes

AF:

0.0467

AC:

11534

AN:

246924

Hom.:

549

AF XY:

0.0466

AC XY:

6256

AN XY:

134352

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.00734

Gnomad ASJ exome

AF:

0.00432

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00494

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0742

Gnomad OTH exome

AF:

0.0394

GnomAD4 exome

AF:

0.0587

AC:

85875

AN:

1461708

Hom.:

3270

Cov.:

AF XY:

0.0570

AC XY:

41420

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.00905

Gnomad4 AMR exome

AF:

0.00778

Gnomad4 ASJ exome

AF:

0.00494

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00452

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0686

Gnomad4 OTH exome

AF:

0.0413

GnomAD4 genome

AF:

0.0481

AC:

6827

AN:

142014

Hom.:

251

Cov.:

AF XY:

0.0476

AC XY:

3297

AN XY:

69256

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.0161

Gnomad4 ASJ

AF:

0.00766

Gnomad4 EAS

AF:

0.000200

Gnomad4 SAS

AF:

0.00492

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.0742

Gnomad4 OTH

AF:

0.0238

Alfa

AF:

0.0558

Hom.:

630

Bravo

AF:

0.0365

TwinsUK

AF:

0.0787

AC:

292

ALSPAC

AF:

0.0729

AC:

281

ESP6500AA

AF:

0.0165

AC:

ESP6500EA

AF:

0.0666

AC:

361

ExAC

AF:

0.0507

AC:

6108

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0528

EpiControl

AF:

0.0521

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

Oct 21, 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

0.15

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.5

DANN

Benign

0.97

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Benign

0.33

Sift4G

Pathogenic

0.0

Polyphen

0.84

Vest4

0.054

MPC

0.84

ClinPred

0.0052

GERP RS

0.35

Varity_R

0.022

gMVP

0.072

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

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