NM_207037.2:c.148+275G>A

Variant names:

• chr15-56921373-G-A
• rs213152
• NM_207037.2:c.148+275G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207037.2(TCF12):​c.148+275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,706 control chromosomes in the GnomAD database, including 2,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2988 hom., cov: 31)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57
• 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: 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-56921373-G-A is Benign according to our data. Variant chr15-56921373-G-A is described in ClinVar as Benign. ClinVar VariationId is 1231595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 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.148+275G>A		intron	N/A	NP_996920.1	Q99081-3
	TCF12	NM_001322151.2		c.148+275G>A		intron	N/A	NP_001309080.1	Q99081-3
	TCF12	NM_001322159.3		c.148+275G>A		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.148+275G>A		intron	N/A	ENSP00000331057.6	Q99081-3
	TCF12	ENST00000267811.9	TSL:1	c.148+275G>A		intron	N/A	ENSP00000267811.5	Q99081-1
	TCF12	ENST00000557843.5	TSL:1	c.148+275G>A		intron	N/A	ENSP00000453737.1	Q99081-1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27615 AN: 151588 Hom.: 2991 Cov.: 31

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.182 AC: 27615 AN: 151706 Hom.: 2988 Cov.: 31 AF XY: 0.181 AC XY: 13423 AN XY: 74132

African (AFR) AF: 0.0684 AC: 2835 AN: 41462

American (AMR) AF: 0.213 AC: 3247 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3462

East Asian (EAS) AF: 0.183 AC: 946 AN: 5170

South Asian (SAS) AF: 0.197 AC: 948 AN: 4814

European-Finnish (FIN) AF: 0.222 AC: 2327 AN: 10486

Middle Eastern (MID) AF: 0.210 AC: 61 AN: 290

European-Non Finnish (NFE) AF: 0.239 AC: 16188 AN: 67746

Other (OTH) AF: 0.193 AC: 407 AN: 2110

Alfa AF: 0.200 Hom.: 452

Bravo AF: 0.174

Asia WGS AF: 0.175 AC: 599 AN: 3426

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.24
PhyloP100		-1.6
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: rs213152; hg19: chr15-57213571;