17-15740138-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388465.1(TBC1D26):c.536C>T(p.Ala179Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TBC1D26
NM_001388465.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

TBC1D26 (HGNC:28745): (TBC1 domain family member 26) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D26 links:

ZNF286A-TBC1D26 (HGNC:55384): (ZNF286A-TBC1D26 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ZNF286A and TBC1D26 genes. This transcript is thought to be non-coding because it would be subject to nonsense-mediated mRNA decay (NMD). [provided by RefSeq, Nov 2020]

ZNF286A-TBC1D26 links:

TBC1D26-AS1 (HGNC:41211): (TBC1D26 antisense RNA 1)

TBC1D26-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12828803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D26	NM_001388465.1 link	c.536C>T	p.Ala179Val	missense_variant	Exon 9 of 15	ENST00000437605.4	NP_001375394.1
TBC1D26	NM_178571.4 link	c.536C>T	p.Ala179Val	missense_variant	Exon 9 of 15		NP_848666.2	Q86UD7
ZNF286A-TBC1D26	NR_171000.1 link	n.2725C>T		non_coding_transcript_exon_variant	Exon 16 of 23
TBC1D26-AS1	XR_001753084.3 link	n.149+3465G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBC1D26	ENST00000437605.4 link	c.536C>T	p.Ala179Val	missense_variant	Exon 9 of 15	5	NM_001388465.1	ENSP00000410111.3	A0A8J8ZQP4
ZNF286A-TBC1D26	ENST00000413242.6 link	n.*1300C>T		non_coding_transcript_exon_variant	Exon 11 of 17	2		ENSP00000458062.1
ZNF286A-TBC1D26	ENST00000413242.6 link	n.*1300C>T		3_prime_UTR_variant	Exon 11 of 17	2		ENSP00000458062.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249560

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.0000646

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000263

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.536C>T (p.A179V) alteration is located in exon 9 (coding exon 7) of the TBC1D26 gene. This alteration results from a C to T substitution at nucleotide position 536, causing the alanine (A) at amino acid position 179 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.98

DANN

Benign

0.70

DEOGEN2

Benign

0.0012

.;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.79

T;D;.

M_CAP

Benign

0.0027

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.53

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.93

.;N;.

REVEL

Benign

0.14

Sift

Benign

1.0

.;T;.

Sift4G

Benign

0.30

T;T;T

Polyphen

0.97

D;P;D

Vest4

0.10

MVP

0.20

MPC

0.60

ClinPred

0.14

GERP RS

-1.1

Varity_R

0.046

gMVP

0.088

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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