NM_012338.4:c.765G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012338.4(TSPAN12):c.765G>T(p.Pro255Pro) 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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.215

Publications

28 publications found

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 Gene-Disease associations (from GenCC):

exudative vitreoretinopathy 5
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
TSPAN12-related vitreoretinopathy
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
exudative vitreoretinopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TSPAN12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 rank	MANE	Protein	UniProt
TSPAN12	NM_012338.4 link	c.765G>T	p.Pro255Pro	synonymous_variant	Exon 8 of 8	ENST00000222747.8	NP_036470.1	O95859-1A0A024R740

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSPAN12	ENST00000222747.8 link	c.765G>T	p.Pro255Pro	synonymous_variant	Exon 8 of 8	1	NM_012338.4	ENSP00000222747.3	O95859-1
TSPAN12	ENST00000415871.5 link	c.765G>T	p.Pro255Pro	synonymous_variant	Exon 9 of 9	5		ENSP00000397699.1	O95859-1
TSPAN12	ENST00000450414.5 link	n.*615G>T		non_coding_transcript_exon_variant	Exon 6 of 6	5		ENSP00000397411.1	H7C0X9
TSPAN12	ENST00000450414.5 link	n.*615G>T		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000397411.1	H7C0X9

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

GnomAD2 exomes

AF:

0.801

AC:

201370

AN:

251340

AF XY:

0.805

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 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

African (AFR)

AF:

0.784

AC:

26253

AN:

33478

American (AMR)

AF:

0.838

AC:

37497

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.815

AC:

21308

AN:

26134

East Asian (EAS)

AF:

0.969

AC:

38456

AN:

39696

South Asian (SAS)

AF:

0.903

AC:

77901

AN:

86256

European-Finnish (FIN)

AF:

0.675

AC:

36054

AN:

53416

Middle Eastern (MID)

AF:

0.882

AC:

5089

AN:

5768

European-Non Finnish (NFE)

AF:

0.746

AC:

829553

AN:

1111956

Other (OTH)

AF:

0.785

AC:

47388

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16465

32929

49394

65858

82323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.780

AC:

118605

AN:

152054

Hom.:

46556

Cov.:

AF XY:

0.781

AC XY:

58029

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.785

AC:

32555

AN:

41454

American (AMR)

AF:

0.846

AC:

12931

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

2860

AN:

3472

East Asian (EAS)

AF:

0.955

AC:

4938

AN:

5170

South Asian (SAS)

AF:

0.908

AC:

4384

AN:

4826

European-Finnish (FIN)

AF:

0.657

AC:

6924

AN:

10536

Middle Eastern (MID)

AF:

0.898

AC:

264

AN:

294

European-Non Finnish (NFE)

AF:

0.755

AC:

51338

AN:

67994

Other (OTH)

AF:

0.792

AC:

1674

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1335

2670

4006

5341

6676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.772

Hom.:

86289

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30747064) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Exudative vitreoretinopathy 5

Benign:2

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.54

PhyloP100

-0.21

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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NM_012338.4:c.765G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over