rs1554403626

chr7-120838843-G-GAAACAGC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_012338.4(TSPAN12):c.218_219insGCTGTTT(p.Phe73LeufsTer46) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPAN12 NM_012338.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 7.94

Genes affected

TSPAN12 (HGNC:21641): (tetraspanin 12) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-120838843-G-GAAACAGC is Pathogenic according to our data. Variant chr7-120838843-G-GAAACAGC is described in ClinVar as [Pathogenic]. Clinvar id is 321.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN12	NM_012338.4	c.218_219insGCTGTTT	p.Phe73LeufsTer46	frameshift_variant	4/8	ENST00000222747.8
TSPAN12	XM_005250239.4	c.218_219insGCTGTTT	p.Phe73LeufsTer46	frameshift_variant	5/9
TSPAN12	XM_047420095.1	c.218_219insGCTGTTT	p.Phe73LeufsTer46	frameshift_variant	5/9
TSPAN12	XM_047420096.1	c.218_219insGCTGTTT	p.Phe73LeufsTer47	frameshift_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN12	ENST00000222747.8	c.218_219insGCTGTTT	p.Phe73LeufsTer46	frameshift_variant	4/8	1	NM_012338.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Exudative vitreoretinopathy 5 Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Feb 12, 2010	- -
Pathogenic, criteria provided, single submitter	clinical testing	Genetics and Molecular Pathology, SA Pathology	Oct 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554403626; hg19: chr7-120478897;