rs35615435

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_207037.2(TCF12):c.135A>G(p.Gln45Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,608,830 control chromosomes in the GnomAD database, including 2,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 329 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1829 hom. )

Consequence

TCF12
NM_207037.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.32

Publications

7 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: 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

TCF12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 15-56921085-A-G is Benign according to our data. Variant chr15-56921085-A-G is described in ClinVar as Benign. ClinVar VariationId is 263277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF12	NM_207037.2 link	c.135A>G	p.Gln45Gln	synonymous_variant	Exon 3 of 21	ENST00000333725.10	NP_996920.1	Q99081-3A0A024R5Z0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF12	ENST00000333725.10 link	c.135A>G	p.Gln45Gln	synonymous_variant	Exon 3 of 21	1	NM_207037.2	ENSP00000331057.6		Q99081-3

Frequencies

GnomAD3 genomes

AF:

0.0336

AC:

5117

AN:

152126

Hom.:

328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0659

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.0545

Gnomad FIN

AF:

0.0192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.0249

GnomAD2 exomes

AF:

0.0382

AC:

9519

AN:

248886

AF XY:

0.0360

show subpopulations

Gnomad AFR exome

AF:

0.0664

Gnomad AMR exome

AF:

0.0294

Gnomad ASJ exome

AF:

0.00518

Gnomad EAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.0172

Gnomad NFE exome

AF:

0.00168

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0147

AC:

21383

AN:

1456586

Hom.:

1829

Cov.:

AF XY:

0.0153

AC XY:

11090

AN XY:

724586

show subpopulations

African (AFR)

AF:

0.0622

AC:

2072

AN:

33332

American (AMR)

AF:

0.0265

AC:

1170

AN:

44152

Ashkenazi Jewish (ASJ)

AF:

0.00584

AC:

152

AN:

26022

East Asian (EAS)

AF:

0.277

AC:

10870

AN:

39276

South Asian (SAS)

AF:

0.0446

AC:

3803

AN:

85340

European-Finnish (FIN)

AF:

0.0157

AC:

833

AN:

53200

Middle Eastern (MID)

AF:

0.00643

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000849

AC:

942

AN:

1109376

Other (OTH)

AF:

0.0250

AC:

1504

AN:

60132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

757

1513

2270

3026

3783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0336

AC:

5121

AN:

152244

Hom.:

329

Cov.:

AF XY:

0.0361

AC XY:

2691

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0659

AC:

2736

AN:

41546

American (AMR)

AF:

0.0167

AC:

256

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.288

AC:

1497

AN:

5192

South Asian (SAS)

AF:

0.0541

AC:

261

AN:

4824

European-Finnish (FIN)

AF:

0.0192

AC:

204

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00144

AC:

AN:

67990

Other (OTH)

AF:

0.0247

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

223

446

670

893

1116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0116

Hom.:

Bravo

AF:

0.0367

Asia WGS

AF:

0.133

AC:

464

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.8

(source)

DANN

Benign

0.84

PhyloP100

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over