Variant 8-142741199-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PP3_ModeratePP5_Moderate

The NM_020427.3(SLURP1):c.256G>A(p.Gly86Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,609,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SLURP1
NM_020427.3 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: -0.459

Variant links:

Genes affected

SLURP1 (HGNC:18746): (secreted LY6/PLAUR domain containing 1) The protein encoded by this gene is a member of the Ly6/uPAR family but lacks a GPI-anchoring signal sequence. It is thought that this secreted protein contains antitumor activity. Mutations in this gene have been associated with Mal de Meleda, a rare autosomal recessive skin disorder. This gene maps to the same chromosomal region as several members of the Ly6/uPAR family of glycoprotein receptors. [provided by RefSeq, Jul 2008]

SLURP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a chain Secreted Ly-6/uPAR-related protein 1 (size 80) in uniprot entity SLUR1_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_020427.3

PP3

MetaRNN computational evidence supports a deleterious effect, 0.932

PP5

Variant 8-142741199-C-T is Pathogenic according to our data. Variant chr8-142741199-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 4602.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-142741199-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLURP1	NM_020427.3 linkuse as main transcript	c.256G>A	p.Gly86Arg	missense_variant	3/3	ENST00000246515.2	NP_065160.1	P55000

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLURP1	ENST00000246515.2 linkuse as main transcript	c.256G>A	p.Gly86Arg	missense_variant	3/3	1	NM_020427.3	ENSP00000246515.1		P55000

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000448

AC:

AN:

245774

Hom.:

AF XY:

0.0000598

AC XY:

AN XY:

133682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000600

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1457826

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725308

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000331

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000413

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Acroerythrokeratoderma

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 01, 2003	- -
Pathogenic, no assertion criteria provided	clinical testing	Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University	-	- -

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

SLURP1: PP1:Strong, PM2, PM3, PP4, PS3:Supporting, PS4:Supporting -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

0.0086

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.60

Eigen

Benign

-0.018

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.49

Sift

Benign

0.095

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.89

MutPred

0.92

Gain of solvent accessibility (P = 0.0042);

MVP

0.85

MPC

0.83

ClinPred

0.84

GERP RS

3.8

Varity_R

0.45

gMVP

0.80

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