chr15-57287318-A-G

Variant names:

• chr15-57287318-A-G
• rs12438324
• NM_207037.2:c.*1173A>G

Variant summary

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

The NM_207037.2(TCF12):​c.*1173A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 152,750 control chromosomes in the GnomAD database, including 368 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 0.040 (368 hom., cov: 33)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: TCF12 NM_207037.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 5 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, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

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.*1173A>G		3_prime_UTR	Exon 21 of 21	NP_996920.1	Q99081-3
	TCF12	NM_001322151.2		c.*1173A>G		3_prime_UTR	Exon 21 of 21	NP_001309080.1	Q99081-3
	TCF12	NM_001322162.2		c.*1173A>G		3_prime_UTR	Exon 21 of 21	NP_001309091.1	Q99081-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF12	ENST00000333725.10	TSL:1 MANE Select	c.*1173A>G		3_prime_UTR	Exon 21 of 21	ENSP00000331057.6	Q99081-3
	TCF12	ENST00000267811.9	TSL:1	c.*1173A>G		3_prime_UTR	Exon 20 of 20	ENSP00000267811.5	Q99081-1
	TCF12	ENST00000557843.5	TSL:1	c.*1173A>G		3_prime_UTR	Exon 20 of 20	ENSP00000453737.1	Q99081-1

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6111 AN: 152172 Hom.: 365 Cov.: 33

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0487

GnomAD4 exome AF: 0.0498 AC: 23 AN: 462 Hom.: 0 Cov.: 0 AF XY: 0.0429 AC XY: 12 AN XY: 280

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0469 AC: 20 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0714 AC: 2 AN: 28

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0402 AC: 6124 AN: 152288 Hom.: 368 Cov.: 33 AF XY: 0.0418 AC XY: 3111 AN XY: 74470

African (AFR) AF: 0.0111 AC: 460 AN: 41586

American (AMR) AF: 0.167 AC: 2552 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5184

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4826

European-Finnish (FIN) AF: 0.0323 AC: 343 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0343 AC: 2332 AN: 68012

Other (OTH) AF: 0.0482 AC: 102 AN: 2116

Alfa AF: 0.0420 Hom.: 455

Bravo AF: 0.0506

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12438324; hg19: chr15-57579516;