Variant 6-31161839-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007109.3(TCF19):c.631A>G(p.Met211Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,611,980 control chromosomes in the GnomAD database, including 457,232 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.78 ( 46614 hom., cov: 35)

Exomes 𝑓: 0.75 ( 410618 hom. )

Consequence

TCF19
NM_007109.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0155858E-6).

BP6

Variant 6-31161839-A-G is Benign according to our data. Variant chr6-31161839-A-G is described in ClinVar as [Benign]. Clinvar id is 1181041.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF19	NM_007109.3 linkuse as main transcript	c.631A>G	p.Met211Val	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.631A>G	p.Met211Val	missense_variant	3/4	1	NM_007109.3	P1

Frequencies

GnomAD3 genomes

AF:

0.780

AC:

118742

AN:

152140

Hom.:

46575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.806

Gnomad AMR

AF:

0.805

Gnomad ASJ

AF:

0.862

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.749

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.748

Gnomad OTH

AF:

0.816

GnomAD3 exomes

AF:

0.752

AC:

183042

AN:

243358

Hom.:

69338

AF XY:

0.752

AC XY:

100128

AN XY:

133230

show subpopulations

Gnomad AFR exome

AF:

0.847

Gnomad AMR exome

AF:

0.761

Gnomad ASJ exome

AF:

0.859

Gnomad EAS exome

AF:

0.699

Gnomad SAS exome

AF:

0.703

Gnomad FIN exome

AF:

0.742

Gnomad NFE exome

AF:

0.750

Gnomad OTH exome

AF:

0.772

GnomAD4 exome

AF:

0.749

AC:

1092964

AN:

1459722

Hom.:

410618

Cov.:

AF XY:

0.748

AC XY:

542922

AN XY:

726124

show subpopulations

Gnomad4 AFR exome

AF:

0.851

Gnomad4 AMR exome

AF:

0.771

Gnomad4 ASJ exome

AF:

0.858

Gnomad4 EAS exome

AF:

0.647

Gnomad4 SAS exome

AF:

0.712

Gnomad4 FIN exome

AF:

0.741

Gnomad4 NFE exome

AF:

0.748

Gnomad4 OTH exome

AF:

0.764

GnomAD4 genome

AF:

0.780

AC:

118835

AN:

152258

Hom.:

46614

Cov.:

AF XY:

0.779

AC XY:

58016

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.847

Gnomad4 AMR

AF:

0.805

Gnomad4 ASJ

AF:

0.862

Gnomad4 EAS

AF:

0.678

Gnomad4 SAS

AF:

0.687

Gnomad4 FIN

AF:

0.749

Gnomad4 NFE

AF:

0.748

Gnomad4 OTH

AF:

0.816

Alfa

AF:

0.764

Hom.:

79213

Bravo

AF:

0.790

TwinsUK

AF:

0.737

AC:

2734

ALSPAC

AF:

0.750

AC:

2891

ESP6500AA

AF:

0.863

AC:

2183

ESP6500EA

AF:

0.757

AC:

3834

ExAC

AF:

0.751

AC:

87316

Asia WGS

AF:

0.755

AC:

2626

AN:

3478

EpiCase

AF:

0.768

EpiControl

AF:

0.781

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 13, 2018

This variant is associated with the following publications: (PMID: 29632382) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.1

DANN

Benign

0.48

DEOGEN2

Benign

0.00089

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0020

MetaRNN

Benign

0.0000010

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.2

N;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

0.35

N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.82

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.012

MPC

0.51

ClinPred

0.0048

GERP RS

4.5

Varity_R

0.039

gMVP

0.093

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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