Genetic Variant NM_014068.3:c.127C>T (chr6-31138739-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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

Publications

15 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: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PSORS1C1	NM_014068.3 link	c.127C>T	p.Pro43Ser	missense_variant	Exon 5 of 6	ENST00000259881.10	NP_054787.2	Q9UIG5-1D2IYL0
PSORS1C2	NM_014069.3 link	c.55+233G>A		intron_variant	Intron 1 of 1	ENST00000259845.5	NP_054788.2	Q9UIG4A0A1U9X9A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSORS1C1	ENST00000259881.10 link	c.127C>T	p.Pro43Ser	missense_variant	Exon 5 of 6	1	NM_014068.3	ENSP00000259881.9		Q9UIG5-1
PSORS1C2	ENST00000259845.5 link	c.55+233G>A		intron_variant	Intron 1 of 1	1	NM_014069.3	ENSP00000259845.4		Q9UIG4

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

GnomAD2 exomes

AF:

0.0462

AC:

11487

AN:

248662

AF XY:

0.0441

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 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

African (AFR)

AF:

0.139

AC:

4647

AN:

33478

American (AMR)

AF:

0.0247

AC:

1106

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0287

AC:

751

AN:

26134

East Asian (EAS)

AF:

0.178

AC:

7063

AN:

39698

South Asian (SAS)

AF:

0.0362

AC:

3125

AN:

86258

European-Finnish (FIN)

AF:

0.0578

AC:

3089

AN:

53398

Middle Eastern (MID)

AF:

0.0319

AC:

184

AN:

5768

European-Non Finnish (NFE)

AF:

0.0234

AC:

26059

AN:

1111988

Other (OTH)

AF:

0.0467

AC:

2823

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2813

5626

8438

11251

14064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1182

2364

3546

4728

5910

<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:

0.0633

AC:

9623

AN:

152112

Hom.:

498

Cov.:

AF XY:

0.0643

AC XY:

4784

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.136

AC:

5640

AN:

41468

American (AMR)

AF:

0.0342

AC:

522

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

AN:

3466

East Asian (EAS)

AF:

0.157

AC:

810

AN:

5160

South Asian (SAS)

AF:

0.0415

AC:

200

AN:

4814

European-Finnish (FIN)

AF:

0.0529

AC:

560

AN:

10594

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0241

AC:

1641

AN:

68016

Other (OTH)

AF:

0.0631

AC:

133

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

426

851

1277

1702

2128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0370

Hom.:

580

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

Dec 09, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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

PhyloP100

-0.28

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

PromoterAI

-0.0030

Neutral

(source)

Varity_R

0.024

gMVP

0.034

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over