Variant 6-31161765-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_007109.3(TCF19):c.557G>A(p.Arg186Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,600,312 control chromosomes in the GnomAD database, including 19 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 (★).

Frequency

Genomes: 𝑓 0.0059 ( 12 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 7 hom. )

Consequence

TCF19
NM_007109.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.773

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=0.0014848709).

BP6

Variant 6-31161765-G-A is Benign according to our data. Variant chr6-31161765-G-A is described in ClinVar as [Benign]. Clinvar id is 714312.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0059 (898/152312) while in subpopulation AFR AF= 0.0191 (792/41556). AF 95% confidence interval is 0.018. There are 12 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF19	NM_007109.3 linkuse as main transcript	c.557G>A	p.Arg186Gln	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.557G>A	p.Arg186Gln	missense_variant	3/4	1	NM_007109.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00590

AC:

898

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00152

AC:

356

AN:

234754

Hom.:

AF XY:

0.00120

AC XY:

154

AN XY:

128106

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000106

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.00105

GnomAD4 exome

AF:

0.000791

AC:

1146

AN:

1448000

Hom.:

Cov.:

AF XY:

0.000758

AC XY:

545

AN XY:

719060

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.00185

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000154

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000321

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00590

AC:

898

AN:

152312

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

402

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0191

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.00705

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0174

AC:

ESP6500EA

AF:

0.000394

AC:

ExAC

AF:

0.00167

AC:

195

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.7

DANN

Benign

0.81

DEOGEN2

Benign

0.00045

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.013

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.23

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.14

N;N;N

REVEL

Benign

0.086

Sift

Benign

0.67

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.030

MVP

0.076

MPC

0.58

ClinPred

0.0013

GERP RS

-7.2

Varity_R

0.026

gMVP

0.089

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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