dbSNP rs34560099: TCF12:p.Pro99Pro (chr15-57091863-A-G) – ACMG Classification: Benign (-21 pts)

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.297A>G(p.Pro99Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,613,736 control chromosomes in the GnomAD database, including 830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 375 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 455 hom. )

Consequence

TCF12
NM_207037.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.01

Publications

1 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 15-57091863-A-G is Benign according to our data. Variant chr15-57091863-A-G is described in ClinVar as Benign. ClinVar VariationId is 263280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 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	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF12	NM_207037.2	MANE Select	c.297A>G	p.Pro99Pro	synonymous	Exon 5 of 21	NP_996920.1	Q99081-3
TCF12	NM_001322151.2		c.297A>G	p.Pro99Pro	synonymous	Exon 5 of 21	NP_001309080.1	Q99081-3
TCF12	NM_001322159.3		c.297A>G	p.Pro99Pro	synonymous	Exon 5 of 21	NP_001309088.1	Q99081-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF12	ENST00000333725.10	TSL:1 MANE Select	c.297A>G	p.Pro99Pro	synonymous	Exon 5 of 21	ENSP00000331057.6	Q99081-3
TCF12	ENST00000267811.9	TSL:1	c.297A>G	p.Pro99Pro	synonymous	Exon 5 of 20	ENSP00000267811.5	Q99081-1
TCF12	ENST00000557843.5	TSL:1	c.297A>G	p.Pro99Pro	synonymous	Exon 5 of 20	ENSP00000453737.1	Q99081-1

Frequencies

GnomAD3 genomes

AF:

0.0422

AC:

6427

AN:

152182

Hom.:

373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00312

Gnomad OTH

AF:

0.0368

GnomAD2 exomes

AF:

0.0141

AC:

3553

AN:

251234

AF XY:

0.0110

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.0291

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.00695

AC:

10160

AN:

1461436

Hom.:

455

Cov.:

AF XY:

0.00643

AC XY:

4671

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.152

AC:

5076

AN:

33446

American (AMR)

AF:

0.0152

AC:

681

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0295

AC:

771

AN:

26118

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39678

South Asian (SAS)

AF:

0.000626

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.0269

AC:

155

AN:

5762

European-Non Finnish (NFE)

AF:

0.00225

AC:

2496

AN:

1111716

Other (OTH)

AF:

0.0152

AC:

920

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

444

888

1331

1775

2219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<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:

0.0422

AC:

6433

AN:

152300

Hom.:

375

Cov.:

AF XY:

0.0417

AC XY:

3106

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.135

AC:

5620

AN:

41544

American (AMR)

AF:

0.0268

AC:

410

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00310

AC:

211

AN:

68022

Other (OTH)

AF:

0.0379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

284

569

853

1138

1422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0230

Hom.:

110

Bravo

AF:

0.0482

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00508

EpiControl

AF:

0.00427

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over