8-142741212-G-T

Position:

• chr8-142741212-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP5

The NM_020427.3(SLURP1):​c.243C>A​(p.Asp81Glu) 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 1,458,026 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.607

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 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
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-142741212-G-T is Pathogenic according to our data. Variant chr8-142741212-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 2504644.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLURP1	NM_020427.3	c.243C>A	p.Asp81Glu	missense_variant	3/3	ENST00000246515.2	NP_065160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLURP1	ENST00000246515.2	c.243C>A	p.Asp81Glu	missense_variant	3/3	1	NM_020427.3	ENSP00000246515.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458026 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725404

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Acroerythrokeratoderma Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.013	D
Sift4G	Benign	0.18	T
Polyphen		0.99	D
Vest4		0.22
MutPred		0.60		Loss of sheet (P = 0.0457);
MVP		0.85
MPC		0.80
ClinPred		0.92	D
GERP RS		3.8
Varity_R		0.18
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-143822630;