Genetic Variant TCF19:p.Leu94Met (chr6-31161488-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 14/22 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04293096).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007109.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF19	NM_007109.3	MANE Select	c.280C>A	p.Leu94Met	missense	Exon 3 of 4	NP_009040.2	A0A1U9X8M7
TCF19	NM_001077511.2		c.280C>A	p.Leu94Met	missense	Exon 3 of 4	NP_001070979.1	A0A1U9X8M7
TCF19	NM_001318908.2		c.280C>A	p.Leu94Met	missense	Exon 4 of 5	NP_001305837.1	Q9Y242

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF19	ENST00000376257.8	TSL:1 MANE Select	c.280C>A	p.Leu94Met	missense	Exon 3 of 4	ENSP00000365433.3	Q9Y242
TCF19	ENST00000376255.4	TSL:1	c.280C>A	p.Leu94Met	missense	Exon 3 of 4	ENSP00000365431.4	Q9Y242
TCF19	ENST00000706778.1		c.280C>A	p.Leu94Met	missense	Exon 4 of 5	ENSP00000516543.1	Q9Y242

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

GnomAD2 exomes

AF:

0.000104

AC:

AN:

154204

AF XY:

0.0000718

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 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

African (AFR)

AF:

0.00200

AC:

AN:

28554

American (AMR)

AF:

0.0000397

AC:

AN:

25188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19260

East Asian (EAS)

AF:

0.00

AC:

AN:

35790

South Asian (SAS)

AF:

0.0000462

AC:

AN:

64872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48620

Middle Eastern (MID)

AF:

0.000384

AC:

AN:

5214

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1048908

Other (OTH)

AF:

0.000239

AC:

AN:

54428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000223

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.000748

AC:

AN:

41454

American (AMR)

AF:

0.000131

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000234

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Benign

0.11

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.64

M_CAP

Benign

0.017

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.69

PhyloP100

0.74

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.11

REVEL

Benign

0.17

Sift

Benign

0.21

Sift4G

Benign

0.23

Polyphen

0.88

Vest4

0.28

MVP

0.66

MPC

1.4

ClinPred

0.076

GERP RS

3.8

PromoterAI

0.013

Neutral

(source)

Varity_R

0.16

gMVP

0.23

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over