rs267607154

Variant names:

• chr7-120788801-C-G
• rs267607154
• NM_012338.4:c.709G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-120788801-C-G
• chr7-120788801-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1 PM2 PP3_Strong PP5

The NM_012338.4(TSPAN12):​c.709G>C​(p.Ala237Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: TSPAN12 NM_012338.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.38

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 9 ACMG points.

• PM1: In a transmembrane_region Helical (size 20) in uniprot entity TSN12_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_012338.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.959
• PP5: Variant 7-120788801-C-G is Pathogenic according to our data. Variant chr7-120788801-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 319.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-120788801-C-G is described in Lovd as [Likely_pathogenic]. Variant chr7-120788801-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN12	NM_012338.4	c.709G>C	p.Ala237Pro	missense_variant	Exon 8 of 8	ENST00000222747.8	NP_036470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN12	ENST00000222747.8	c.709G>C	p.Ala237Pro	missense_variant	Exon 8 of 8	1	NM_012338.4	ENSP00000222747.3
TSPAN12	ENST00000415871.5	c.709G>C	p.Ala237Pro	missense_variant	Exon 9 of 9	5		ENSP00000397699.1
TSPAN12	ENST00000450414.5	n.*559G>C		non_coding_transcript_exon_variant	Exon 6 of 6	5		ENSP00000397411.1
TSPAN12	ENST00000450414.5	n.*559G>C		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000397411.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Exudative vitreoretinopathy 5 Pathogenic:1

Feb 12, 2010

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D;D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Uncertain	0.094	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	1.6	L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.4	N;N
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.026	D;D
Polyphen		1.0	D;D
Vest4		0.93
MutPred		0.83		Loss of stability (P = 0.0653);Loss of stability (P = 0.0653);
MVP		0.86
MPC		0.63
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.96
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs267607154; hg19: chr7-120428855;