Genetic Variant NM_207037.2:c.130A>G (chr15-56921080-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207037.2(TCF12):c.130A>G(p.Ser44Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TCF12
NM_207037.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17323935).

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.130A>G	p.Ser44Gly	missense	Exon 3 of 21	NP_996920.1	Q99081-3
TCF12	NM_001322151.2		c.130A>G	p.Ser44Gly	missense	Exon 3 of 21	NP_001309080.1	Q99081-3
TCF12	NM_001322159.3		c.130A>G	p.Ser44Gly	missense	Exon 3 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.130A>G	p.Ser44Gly	missense	Exon 3 of 21	ENSP00000331057.6	Q99081-3
TCF12	ENST00000267811.9	TSL:1	c.130A>G	p.Ser44Gly	missense	Exon 3 of 20	ENSP00000267811.5	Q99081-1
TCF12	ENST00000557843.5	TSL:1	c.130A>G	p.Ser44Gly	missense	Exon 3 of 20	ENSP00000453737.1	Q99081-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724874

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26022

East Asian (EAS)

AF:

0.00

AC:

AN:

39416

South Asian (SAS)

AF:

0.00

AC:

AN:

85500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109462

Other (OTH)

AF:

0.00

AC:

AN:

60162

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.12

Eigen

Benign

-0.071

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0064

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

4.2

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.56

REVEL

Benign

0.077

Sift

Benign

0.80

Sift4G

Benign

0.49

Polyphen

0.0020

Vest4

0.35

MutPred

0.12

Gain of glycosylation at S43 (P = 0.0205)

MVP

0.59

MPC

0.52

ClinPred

0.84

GERP RS

5.0

Varity_R

0.20

gMVP

0.43

Mutation Taster

=58/42

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over