ENST00000560836.1:c.*12-3021C>G

Variant names:

• chr15-57296205-C-G
• rs10518907
• ENST00000560836.1:c.*12-3021C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000560836.1(TCF12):​c.*12-3021C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 152,268 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.027 (293 hom., cov: 33)
• Consequence: TCF12 ENST00000560836.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• TCF12-related craniosynostosis

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen
• hypogonadotropic hypogonadism 26 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Kallmann syndrome

  Inheritance: AD, AR Classification: STRONG Submitted by: Franklin by Genoox
• isolated brachycephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated plagiocephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF12	ENST00000560836.1	c.*12-3021C>G		intron_variant	Intron 1 of 1	3		ENSP00000454823.1

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4039 AN: 152150 Hom.: 291 Cov.: 33

Gnomad AFR AF: 0.00719

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.0368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0266 AC: 4050 AN: 152268 Hom.: 293 Cov.: 33 AF XY: 0.0281 AC XY: 2092 AN XY: 74454

African (AFR) AF: 0.00717 AC: 298 AN: 41542

American (AMR) AF: 0.152 AC: 2322 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4828

European-Finnish (FIN) AF: 0.0138 AC: 146 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0157 AC: 1068 AN: 68024

Other (OTH) AF: 0.0365 AC: 77 AN: 2112

Alfa AF: 0.0267 Hom.: 34

Bravo AF: 0.0372

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.63
PhyloP100		-0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10518907; hg19: chr15-57588403;