rs34560099

chr15-57091863-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_207037.2(TCF12):c.297A>G(p.Pro99=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.01

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]

ACMG classification

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/exons	MANE	UniProt
TCF12	NM_207037.2	c.297A>G	p.Pro99=	synonymous_variant	5/21	ENST00000333725.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF12	ENST00000333725.10	c.297A>G	p.Pro99=	synonymous_variant	5/21	1	NM_207037.2	P4

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6427 AN: 152182 Hom.: 373 Cov.: 32

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

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.: 30 AF XY: 0.00643 AC XY: 4671 AN XY: 727000

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.: 32 AF XY: 0.0417 AC XY: 3106 AN XY: 74482

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.: 81

Bravo AF: 0.0482

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.00508

EpiControl AF: 0.00427

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs34560099; hg19: chr15-57384061;