dbSNP rs34560099: TCF12:p.Pro99Pro (chr15-57091863-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_207037.2(TCF12):c.297A>G(p.Pro99Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,613,736 control chromosomes in the GnomAD database, including 830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 375 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 455 hom. )

Consequence

TCF12
NM_207037.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.01

Variant links:

Genes affected

TCF12 (HGNC:11623): (transcription factor 12) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

TCF12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 15-57091863-A-G is Benign according to our data. Variant chr15-57091863-A-G is described in ClinVar as [Benign]. Clinvar id is 263280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-57091863-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF12	NM_207037.2 link	c.297A>G	p.Pro99Pro	synonymous_variant	Exon 5 of 21	ENST00000333725.10	NP_996920.1	Q99081-3A0A024R5Z0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF12	ENST00000333725.10 link	c.297A>G	p.Pro99Pro	synonymous_variant	Exon 5 of 21	1	NM_207037.2	ENSP00000331057.6		Q99081-3

Frequencies

GnomAD3 genomes

AF:

0.0422

AC:

6427

AN:

152182

Hom.:

373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00312

Gnomad OTH

AF:

0.0368

GnomAD3 exomes

AF:

0.0141

AC:

3553

AN:

251234

Hom.:

174

AF XY:

0.0110

AC XY:

1496

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.0291

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.00695

AC:

10160

AN:

1461436

Hom.:

455

Cov.:

AF XY:

0.00643

AC XY:

4671

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.0295

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00225

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.0422

AC:

6433

AN:

152300

Hom.:

375

Cov.:

AF XY:

0.0417

AC XY:

3106

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.0268

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0482

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00508

EpiControl

AF:

0.00427

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 03, 2019

GeneDx

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

- -

not specified

Benign:1

Feb 12, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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