Variant 6-31161488-C-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.280C>A(p.Leu94Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000755 in 1,483,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000059 ( 0 hom. )

Consequence

TCF19
NM_007109.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.745

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:

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=0.04293096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF19	NM_007109.3 linkuse as main transcript	c.280C>A	p.Leu94Met	missense_variant	3/4	ENST00000376257.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF19	ENST00000376257.8 linkuse as main transcript	c.280C>A	p.Leu94Met	missense_variant	3/4	1	NM_007109.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

154204

Hom.:

AF XY:

0.0000718

AC XY:

AN XY:

83510

show subpopulations

Gnomad AFR exome

AF:

0.000958

Gnomad AMR exome

AF:

0.0000619

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000812

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000256

Gnomad OTH exome

AF:

0.000307

GnomAD4 exome

AF:

0.0000586

AC:

AN:

1330834

Hom.:

Cov.:

AF XY:

0.0000506

AC XY:

AN XY:

651662

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.0000397

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000462

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000191

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.000223

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000748

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000176

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000844

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000121

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Apr 22, 2022

The c.280C>A (p.L94M) alteration is located in exon 3 (coding exon 2) of the TCF19 gene. This alteration results from a C to A substitution at nucleotide position 280, causing the leucine (L) at amino acid position 94 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.092

T;T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.35

M_CAP

Benign

0.017

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

0.68

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.11

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.88

P;P;.

Vest4

0.28

MVP

0.66

MPC

1.4

ClinPred

0.076

GERP RS

3.8

Varity_R

0.16

gMVP

0.23

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