Variant chr6-31162544-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007109.3(TCF19):c.865G>A(p.Gly289Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

TCF19
NM_007109.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.247

Variant links:

Genes affected

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TCF19 links:

TCF19 (HGNC:):

TCF19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016195238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF19	NM_007109.3 linkuse as main transcript	c.865G>A	p.Gly289Arg	missense_variant	4/4	ENST00000376257.8	NP_009040.2	Q9Y242A0A1U9X8M7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF19	ENST00000376257.8 linkuse as main transcript	c.865G>A	p.Gly289Arg	missense_variant	4/4	1	NM_007109.3	ENSP00000365433.3		Q9Y242

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000246

AC:

AN:

244192

Hom.:

AF XY:

0.000262

AC XY:

AN XY:

133664

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.000611

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000668

GnomAD4 exome

AF:

0.000202

AC:

295

AN:

1460736

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

154

AN XY:

726692

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000220

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000223

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000247

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000222

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

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

Oct 29, 2024

The c.865G>A (p.G289R) alteration is located in exon 4 (coding exon 3) of the TCF19 gene. This alteration results from a G to A substitution at nucleotide position 865, causing the glycine (G) at amino acid position 289 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

Benign

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0021

T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.021

Sift

Benign

0.099

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0040

B;B

Vest4

0.20

MutPred

0.36

Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);

MVP

0.20

MPC

0.60

ClinPred

0.019

GERP RS

0.95

Varity_R

0.073

gMVP

0.36

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