Variant 4-26735482-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018317.4(TBC1D19):c.1112T>C(p.Met371Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000441 in 1,563,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

TBC1D19
NM_018317.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.48

Variant links:

Genes affected

TBC1D19 (HGNC:25624): (TBC1 domain family member 19) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D19 links:

TBC1D19 (HGNC:):

TBC1D19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D19	NM_018317.4 linkuse as main transcript	c.1112T>C	p.Met371Thr	missense_variant	16/21	ENST00000264866.9	NP_060787.2	Q8N5T2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBC1D19	ENST00000264866.9 linkuse as main transcript	c.1112T>C	p.Met371Thr	missense_variant	16/21	1	NM_018317.4	ENSP00000264866.4	Q8N5T2-1
TBC1D19	ENST00000511789.5 linkuse as main transcript	c.917T>C	p.Met306Thr	missense_variant	13/18	1		ENSP00000425569.1	Q8N5T2-2
TBC1D19	ENST00000502873.5 linkuse as main transcript	n.1222T>C		non_coding_transcript_exon_variant	16/20	1

Frequencies

GnomAD3 genomes

AF:

0.0000594

AC:

AN:

151396

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000962

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000492

AC:

AN:

203216

Hom.:

AF XY:

0.0000184

AC XY:

AN XY:

108896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000101

Gnomad NFE exome

AF:

0.0000921

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000425

AC:

AN:

1412312

Hom.:

Cov.:

AF XY:

0.0000457

AC XY:

AN XY:

700332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000582

Gnomad4 NFE exome

AF:

0.0000490

Gnomad4 OTH exome

AF:

0.0000688

GnomAD4 genome

AF:

0.0000594

AC:

AN:

151396

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

73880

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000962

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000332

AC:

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

Dec 03, 2024

The c.1112T>C (p.M371T) alteration is located in exon 16 (coding exon 16) of the TBC1D19 gene. This alteration results from a T to C substitution at nucleotide position 1112, causing the methionine (M) at amino acid position 371 to be replaced by a threonine (T). 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

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.22

B;.

Vest4

0.96

MVP

0.38

MPC

1.1

ClinPred

0.75

GERP RS

4.5

Varity_R

0.81

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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