rs121908319

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

mal de Meleda
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet
hereditary palmoplantar keratoderma, Gamborg-Nielsen type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
palmoplantar keratosis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SLURP1 links:

ENSG00000253196 (HGNC:58427):

ENSG00000253196 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PM1

In a chain Secreted Ly-6/uPAR-related protein 1 (size 80) in uniprot entity SLUR1_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_020427.3

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 7 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.59094 (below the threshold of 3.09). Trascript score misZ: 0.80412 (below the threshold of 3.09). GenCC associations: The gene is linked to mal de Meleda, palmoplantar keratosis, hereditary palmoplantar keratoderma, Gamborg-Nielsen type.

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 VariationId is 4606.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLURP1	NM_020427.3 link	c.229T>C	p.Cys77Arg	missense_variant	Exon 3 of 3	ENST00000246515.2	NP_065160.1	P55000

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLURP1	ENST00000246515.2 link	c.229T>C	p.Cys77Arg	missense_variant	Exon 3 of 3	1	NM_020427.3	ENSP00000246515.1	P55000
ENSG00000253196	ENST00000839249.1 link	n.448+2742A>G		intron_variant	Intron 1 of 2
ENSG00000253196	ENST00000839250.1 link	n.295+2742A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244504

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.0000224

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5448

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111736

Other (OTH)

AF:

0.00

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Acroerythrokeratoderma

Pathogenic:1

Mar 01, 2004

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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

PhyloP100

2.2

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

Mutation Taster

=76/24

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over