TCF12 p.Leu632Leu

Variant names:

• chr15-57273177-C-C
• ENST00000333725.10:c.

Your query was ambiguous. Multiple possible variants found:

• chr15-57273178--
• chr15-57273180-G-A
• chr15-57273178-T-C
• chr15-57273178-TTG-CTT
• chr15-57273178-TTG-CTC
• chr15-57273178-TTG-CTA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207037.2(TCF12):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14
• Publications: 0 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Genomics England PanelApp
• hypogonadotropic hypogonadism 26 with or without anosmia

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

  Inheritance: AR, AD 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207037.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF12	NM_207037.2	MANE Select	c.		intron	N/A	NP_996920.1	Q99081-3
	TCF12	NM_001322151.2		c.		intron	N/A	NP_001309080.1	Q99081-3
	TCF12	NM_001322159.3		c.		intron	N/A	NP_001309088.1	Q99081-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF12	ENST00000333725.10	TSL:1 MANE Select	c.		exon_region	Exon 19 of 21	ENSP00000331057.6	Q99081-3
	TCF12	ENST00000267811.9	TSL:1	c.		exon_region	Exon 18 of 20	ENSP00000267811.5	Q99081-1
	TCF12	ENST00000557843.5	TSL:1	c.		exon_region	Exon 18 of 20	ENSP00000453737.1	Q99081-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-57565375;