Genetic Variant NM_207037.2:c.*3070T>C (chr15-57289215-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_207037.2(TCF12):c.*3070T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,218 control chromosomes in the GnomAD database, including 3,177 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 0.18 ( 3177 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

TCF12
NM_207037.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.86

Publications

2 publications found

Variant links:

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

TCF12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TCF12	NM_207037.2	MANE Select	c.*3070T>C	3_prime_UTR	Exon 21 of 21	NP_996920.1	Q99081-3
TCF12	NM_001322151.2		c.*3070T>C	3_prime_UTR	Exon 21 of 21	NP_001309080.1	Q99081-3
TCF12	NM_001322162.2		c.*3070T>C	3_prime_UTR	Exon 21 of 21	NP_001309091.1	Q99081-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TCF12	ENST00000333725.10	TSL:1 MANE Select	c.*3070T>C	3_prime_UTR	Exon 21 of 21	ENSP00000331057.6	Q99081-3
TCF12	ENST00000267811.9	TSL:1	c.*3070T>C	3_prime_UTR	Exon 20 of 20	ENSP00000267811.5	Q99081-1
TCF12	ENST00000934194.1		c.*3070T>C	3_prime_UTR	Exon 21 of 21	ENSP00000604253.1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

28019

AN:

152100

Hom.:

3178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0584

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.197

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.184

AC:

28019

AN:

152218

Hom.:

3177

Cov.:

AF XY:

0.184

AC XY:

13672

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0584

AC:

2428

AN:

41560

American (AMR)

AF:

0.221

AC:

3379

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

570

AN:

3472

East Asian (EAS)

AF:

0.183

AC:

947

AN:

5182

South Asian (SAS)

AF:

0.201

AC:

969

AN:

4824

European-Finnish (FIN)

AF:

0.224

AC:

2373

AN:

10588

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16731

AN:

67990

Other (OTH)

AF:

0.198

AC:

419

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1119

2238

3356

4475

5594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.225

Hom.:

2173

Bravo

AF:

0.176

Asia WGS

AF:

0.181

AC:

630

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over