Variant chr15-56921085-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_207037.2(TCF12):c.135A>G(p.Gln45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,608,830 control chromosomes in the GnomAD database, including 2,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 329 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1829 hom. )

Consequence

TCF12
NM_207037.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.32

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=-0.57).

BP6

Variant 15-56921085-A-G is Benign according to our data. Variant chr15-56921085-A-G is described in ClinVar as [Benign]. Clinvar id is 263277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-56921085-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF12	NM_207037.2 linkuse as main transcript	c.135A>G	p.Gln45=	synonymous_variant	3/21	ENST00000333725.10	NP_996920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF12	ENST00000333725.10 linkuse as main transcript	c.135A>G	p.Gln45=	synonymous_variant	3/21	1	NM_207037.2	ENSP00000331057	P4	Q99081-3

Frequencies

GnomAD3 genomes

AF:

0.0336

AC:

5117

AN:

152126

Hom.:

328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0659

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.0545

Gnomad FIN

AF:

0.0192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0382

AC:

9519

AN:

248886

Hom.:

898

AF XY:

0.0360

AC XY:

4847

AN XY:

134634

show subpopulations

Gnomad AFR exome

AF:

0.0664

Gnomad AMR exome

AF:

0.0294

Gnomad ASJ exome

AF:

0.00518

Gnomad EAS exome

AF:

0.300

Gnomad SAS exome

AF:

0.0433

Gnomad FIN exome

AF:

0.0172

Gnomad NFE exome

AF:

0.00168

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0147

AC:

21383

AN:

1456586

Hom.:

1829

Cov.:

AF XY:

0.0153

AC XY:

11090

AN XY:

724586

show subpopulations

Gnomad4 AFR exome

AF:

0.0622

Gnomad4 AMR exome

AF:

0.0265

Gnomad4 ASJ exome

AF:

0.00584

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.0446

Gnomad4 FIN exome

AF:

0.0157

Gnomad4 NFE exome

AF:

0.000849

Gnomad4 OTH exome

AF:

0.0250

GnomAD4 genome

AF:

0.0336

AC:

5121

AN:

152244

Hom.:

329

Cov.:

AF XY:

0.0361

AC XY:

2691

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0659

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.288

Gnomad4 SAS

AF:

0.0541

Gnomad4 FIN

AF:

0.0192

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.0247

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.0367

Asia WGS

AF:

0.133

AC:

464

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.8

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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