Variant 20-610215-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004609.4(TCF15):c.23C>G(p.Pro8Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000488 in 1,023,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

TCF15
NM_004609.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

Variant links:

Genes affected

TCF15 (HGNC:11627): (transcription factor 15) The protein encoded by this gene is found in the nucleus and may be involved in the early transcriptional regulation of patterning of the mesoderm. The encoded basic helix-loop-helix protein requires dimerization with another basic helix-loop-helix protein for efficient DNA binding. [provided by RefSeq, Jul 2008]

TCF15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF15	NM_004609.4 linkuse as main transcript	c.23C>G	p.Pro8Arg	missense_variant	1/2	ENST00000246080.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF15	ENST00000246080.4 linkuse as main transcript	c.23C>G	p.Pro8Arg	missense_variant	1/2	1	NM_004609.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000204

AC:

AN:

146872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000228

AC:

AN:

876782

Hom.:

Cov.:

AF XY:

0.00000242

AC XY:

AN XY:

412724

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000254

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000204

AC:

AN:

146872

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

71452

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000303

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.23C>G (p.P8R) alteration is located in exon 1 (coding exon 1) of the TCF15 gene. This alteration results from a C to G substitution at nucleotide position 23, causing the proline (P) at amino acid position 8 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Benign

0.13

Eigen_PC

Benign

0.098

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.96

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

0.72

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.97

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.6

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0090

Polyphen

0.74

Vest4

0.68

MutPred

0.73

Gain of MoRF binding (P = 2e-04);

MVP

0.66

MPC

2.1

ClinPred

0.97

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.52

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over