8-142741243-C-A

Variant names:

• chr8-142741243-C-A
• rs1448017161
• NM_020427.3:c.212G>T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1 PM2 PP2

The NM_020427.3(SLURP1):​c.212G>T​(p.Arg71Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLURP1 NM_020427.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 7 publications found

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, AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, Orphanet, Ambry Genetics
• hereditary palmoplantar keratoderma, Gamborg-Nielsen type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• palmoplantar keratosis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000253196 (HGNC:58427):

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020427.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLURP1	NM_020427.3	MANE Select	c.212G>T	p.Arg71Leu	missense	Exon 3 of 3	NP_065160.1	P55000

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLURP1	ENST00000246515.2	TSL:1 MANE Select	c.212G>T	p.Arg71Leu	missense	Exon 3 of 3	ENSP00000246515.1	P55000
	ENSG00000253196	ENST00000839249.1		n.448+2759C>A		intron	N/A
	ENSG00000253196	ENST00000839250.1		n.295+2759C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000598 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.19
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.039	D
Polyphen		0.92	P
Vest4		0.42
MutPred		0.68		Loss of disorder (P = 0.045)
MVP		0.77
MPC		0.97
ClinPred		0.97	D
GERP RS		1.8
Varity_R		0.77
gMVP		0.92
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.40		Position offset: -13

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

Other links and lift over

dbSNP: rs1448017161; hg19: chr8-143822661; COSMIC: COSV55816042; COSMIC: COSV55816042;