rs794726655

Positions:

• chr7-120810570-CCTGGT-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_012338.4(TSPAN12):​c.361-5_361-1del variant causes a splice acceptor, splice polypyrimidine tract, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPAN12 NM_012338.4 splice_acceptor, splice_polypyrimidine_tract, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.20

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 Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.11655773 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.2, offset of 7, new splice context is: tttgctttttatcgttccAGtac. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-120810570-CCTGGT-C is Pathogenic according to our data. Variant chr7-120810570-CCTGGT-C is described in ClinVar as [Pathogenic]. Clinvar id is 323.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-120810570-CCTGGT-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN12	NM_012338.4	c.361-5_361-1del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000222747.8	NP_036470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN12	ENST00000222747.8	c.361-5_361-1del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012338.4	ENSP00000222747	P1
TSPAN12	ENST00000415871.5	c.361-5_361-1del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000397699	P1
TSPAN12	ENST00000441017.5	c.361-5_361-1del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		4		ENSP00000411158
TSPAN12	ENST00000450414.5	c.*211-5_*211-1del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000397411

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Exudative vitreoretinopathy 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 12, 2010

- -

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: rs794726655; hg19: chr7-120450624;