Variant chr2-27150298-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_175769.3(TCF23):c.398G>A(p.Gly133Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0022 in 1,613,732 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 6 hom. )

Consequence

TCF23
NM_175769.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

Variant links:

Genes affected

TCF23 (HGNC:18602): (transcription factor 23) The gene encodes a member of the basic helix-loop-helix transcription factor family. Studies of the orthologous gene in mouse have shown the encoded protein does not bind DNA but may negatively regulate other basic helix-loop-helix factors via the formation of a functionally inactive heterodimeric complex. [provided by RefSeq, May 2010]

TCF23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01177904).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF23	NM_175769.3 linkuse as main transcript	c.398G>A	p.Gly133Asp	missense_variant	2/3	ENST00000296096.6
TCF23	XM_005264159.6 linkuse as main transcript	c.398G>A	p.Gly133Asp	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF23	ENST00000296096.6 linkuse as main transcript	c.398G>A	p.Gly133Asp	missense_variant	2/3	1	NM_175769.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00127

AC:

317

AN:

250136

Hom.:

AF XY:

0.00126

AC XY:

171

AN XY:

135520

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.000797

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000879

Gnomad NFE exome

AF:

0.00222

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00228

AC:

3334

AN:

1461416

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1596

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.000698

Gnomad4 NFE exome

AF:

0.00276

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152316

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00251

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.00126

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00120

AC:

146

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00225

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

Aug 16, 2021

The c.398G>A (p.G133D) alteration is located in exon 2 (coding exon 2) of the TCF23 gene. This alteration results from a G to A substitution at nucleotide position 398, causing the glycine (G) at amino acid position 133 to be replaced by an aspartic acid (D). 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

Benign

0.28

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.69

M_CAP

Benign

0.048

MetaRNN

Benign

0.012

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.62

REVEL

Uncertain

0.30

Sift

Benign

0.085

Sift4G

Benign

0.32

Polyphen

0.47

Vest4

0.26

MVP

0.41

MPC

1.3

ClinPred

0.041

GERP RS

4.8

Varity_R

0.080

gMVP

0.41

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