rs12442879

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207037.2(TCF12):c.898G>A(p.Gly300Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,612,244 control chromosomes in the GnomAD database, including 3,004 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 374 hom., cov: 31)

Exomes 𝑓: 0.039 ( 2630 hom. )

Consequence

TCF12
NM_207037.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.41

Publications

22 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015925467).

BP6

Variant 15-57232784-G-A is Benign according to our data. Variant chr15-57232784-G-A is described in ClinVar as Benign. ClinVar VariationId is 263284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF12	NM_207037.2 link	c.898G>A	p.Gly300Ser	missense_variant	Exon 11 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.898G>A	p.Gly300Ser	missense_variant	Exon 11 of 21	1	NM_207037.2	ENSP00000331057.6		Q99081-3

Frequencies

GnomAD3 genomes

AF:

0.0401

AC:

6086

AN:

151674

Hom.:

370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0936

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.0283

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0278

Gnomad FIN

AF:

0.0324

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0343

Gnomad OTH

AF:

0.0484

GnomAD2 exomes

AF:

0.0628

AC:

15703

AN:

250048

AF XY:

0.0538

show subpopulations

Gnomad AFR exome

AF:

0.00923

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.0263

Gnomad EAS exome

AF:

0.00225

Gnomad FIN exome

AF:

0.0388

Gnomad NFE exome

AF:

0.0344

Gnomad OTH exome

AF:

0.0557

GnomAD4 exome

AF:

0.0391

AC:

57090

AN:

1460460

Hom.:

2630

Cov.:

AF XY:

0.0377

AC XY:

27376

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.00740

AC:

247

AN:

33364

American (AMR)

AF:

0.265

AC:

11765

AN:

44462

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

698

AN:

26092

East Asian (EAS)

AF:

0.00111

AC:

AN:

39584

South Asian (SAS)

AF:

0.0301

AC:

2589

AN:

86150

European-Finnish (FIN)

AF:

0.0407

AC:

2171

AN:

53382

Middle Eastern (MID)

AF:

0.0163

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0335

AC:

37270

AN:

1111332

Other (OTH)

AF:

0.0367

AC:

2212

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

2727

5453

8180

10906

13633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1474

2948

4422

5896

7370

<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:

0.0402

AC:

6104

AN:

151784

Hom.:

374

Cov.:

AF XY:

0.0417

AC XY:

3094

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.0110

AC:

455

AN:

41384

American (AMR)

AF:

0.167

AC:

2548

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

AN:

3466

East Asian (EAS)

AF:

0.00232

AC:

AN:

5182

South Asian (SAS)

AF:

0.0277

AC:

133

AN:

4804

European-Finnish (FIN)

AF:

0.0324

AC:

339

AN:

10454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0343

AC:

2330

AN:

67944

Other (OTH)

AF:

0.0493

AC:

104

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

273

546

818

1091

1364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0364

Hom.:

695

Bravo

AF:

0.0505

TwinsUK

AF:

0.0343

AC:

127

ALSPAC

AF:

0.0319

AC:

123

ESP6500AA

AF:

0.0112

AC:

ESP6500EA

AF:

0.0332

AC:

285

ExAC

AF:

0.0542

AC:

6581

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 25, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26264438) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.15

.;T;T;.;T;T;.;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.87

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.66

.;.;T;T;T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;.;N;N;.;.;.

PhyloP100

1.4

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;N;N;N;N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.44

T;T;T;T;T;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T;T;T;T

Polyphen

0.0010

B;P;.;B;P;P;.;D

Vest4

0.057

MPC

0.11

ClinPred

0.0097

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.37

Mutation Taster

=95/5

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

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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