rs41623

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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 (★★).

Frequency

Genomes: 𝑓 0.78 ( 46556 hom., cov: 31)

Exomes 𝑓: 0.77 ( 431492 hom. )

Consequence

TSPAN12
NM_012338.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.215

Variant links:

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]

TSPAN12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
TSPAN12	NM_012338.4 linkuse as main transcript	c.765G>T	p.Pro255=	synonymous_variant	8/8	ENST00000222747.8	NP_036470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN12	ENST00000222747.8 linkuse as main transcript	c.765G>T	p.Pro255=	synonymous_variant	8/8	1	NM_012338.4	ENSP00000222747	P1	O95859-1
TSPAN12	ENST00000415871.5 linkuse as main transcript	c.765G>T	p.Pro255=	synonymous_variant	9/9	5		ENSP00000397699	P1	O95859-1
TSPAN12	ENST00000450414.5 linkuse as main transcript	c.*615G>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	5		ENSP00000397411

Frequencies

GnomAD3 genomes

AF:

0.780

AC:

118513

AN:

151936

Hom.:

46516

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.771

AC XY:

560812

AN XY:

727212

show subpopulations

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.:

AF XY:

0.781

AC XY:

58029

AN XY:

74308

show subpopulations

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:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 30747064) -

Exudative vitreoretinopathy 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
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. -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over