Variant 8-142741226-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5

The NM_020427.3(SLURP1):c.229T>C(p.Cys77Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,990 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 (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLURP1
NM_020427.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.25

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 9 ACMG points.

PM1

In a chain Secreted Ly-6/uPAR-related protein 1 (size 80) in uniprot entity SLUR1_HUMAN there are 15 pathogenic changes around while only 0 benign (100%) in NM_020427.3

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.99

PP5

Variant 8-142741226-A-G is Pathogenic according to our data. Variant chr8-142741226-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 4606.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-142741226-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLURP1	NM_020427.3 linkuse as main transcript	c.229T>C	p.Cys77Arg	missense_variant	3/3	ENST00000246515.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLURP1	ENST00000246515.2 linkuse as main transcript	c.229T>C	p.Cys77Arg	missense_variant	3/3	1	NM_020427.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244504

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133002

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

6.86e-7

AC:

AN:

1457990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725300

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Acroerythrokeratoderma

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Uncertain

0.75

Eigen

Benign

0.10

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.99

MetaSVM

Uncertain

0.47

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

0.90

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.85

MutPred

0.98

Gain of disorder (P = 0.0155);

MVP

0.85

MPC

1.2

ClinPred

1.0

GERP RS

3.8

Varity_R

0.95

gMVP

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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