rs41623

chr7-120788745-C-Achr7-120788745-C-Gchr7-120788745-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_012338.4(TSPAN12):c.765G>T(p.Pro255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 1,613,870 control chromosomes in the GnomAD database, including 478,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P255P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.78 (46556 hom., cov: 31)
  • Exomes 𝑓: 0.77 (431492 hom.)
• Consequence: TSPAN12 NM_012338.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.215

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-120788745-C-A is Benign according to our data. Variant chr7-120788745-C-A is described in ClinVar as [Benign]. Clinvar id is 260253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-120788745-C-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.215 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN12	NM_012338.4	c.765G>T	p.Pro255=	synonymous_variant	8/8	ENST00000222747.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN12	ENST00000222747.8	c.765G>T	p.Pro255=	synonymous_variant	8/8	1	NM_012338.4	P1
TSPAN12	ENST00000415871.5	c.765G>T	p.Pro255=	synonymous_variant	9/9	5		P1
TSPAN12	ENST00000450414.5	c.*615G>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118513 AN: 151936 Hom.: 46516 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.799

GnomAD3 exomes AF: 0.801 AC: 201370 AN: 251340 Hom.: 81466 AF XY: 0.805 AC XY: 109285 AN XY: 135838

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.839

Gnomad ASJ exome AF: 0.821

Gnomad EAS exome AF: 0.957

Gnomad SAS exome AF: 0.905

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.763

Gnomad OTH exome AF: 0.794

GnomAD4 exome AF: 0.766 AC: 1119499 AN: 1461816 Hom.: 431492 Cov.: 77 AF XY: 0.771 AC XY: 560812 AN XY: 727212

Gnomad4 AFR exome AF: 0.784

Gnomad4 AMR exome AF: 0.838

Gnomad4 ASJ exome AF: 0.815

Gnomad4 EAS exome AF: 0.969

Gnomad4 SAS exome AF: 0.903

Gnomad4 FIN exome AF: 0.675

Gnomad4 NFE exome AF: 0.746

Gnomad4 OTH exome AF: 0.785

GnomAD4 genome AF: 0.780 AC: 118605 AN: 152054 Hom.: 46556 Cov.: 31 AF XY: 0.781 AC XY: 58029 AN XY: 74308

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.908

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.792

Alfa AF: 0.770 Hom.: 69906

Bravo AF: 0.794

Asia WGS AF: 0.872 AC: 3029 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Exudative vitreoretinopathy 5 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 30747064) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	1.6
Dann	Benign	0.54

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: rs41623; hg19: chr7-120428799;