dbSNP rs1383446153: TBC1D26:p.Leu82Ile (chr17-15738042-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388465.1(TBC1D26):c.244C>A(p.Leu82Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L82F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

TBC1D26
NM_001388465.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.295

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13023832).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388465.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D26	NM_001388465.1	MANE Select	c.244C>A	p.Leu82Ile	missense	Exon 6 of 15	NP_001375394.1	A0A8J8ZQP4
TBC1D26	NM_178571.4		c.244C>A	p.Leu82Ile	missense	Exon 6 of 15	NP_848666.2	Q86UD7
ZNF286A-TBC1D26	NR_171000.1		n.2433C>A		non_coding_transcript_exon	Exon 13 of 23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D26	ENST00000437605.4	TSL:5 MANE Select	c.244C>A	p.Leu82Ile	missense	Exon 6 of 15	ENSP00000410111.3	A0A8J8ZQP4
ZNF286A-TBC1D26	ENST00000413242.6	TSL:2	n.*806C>A		non_coding_transcript_exon	Exon 9 of 17	ENSP00000458062.1
TBC1D26	ENST00000469477.3	TSL:1	n.244C>A		non_coding_transcript_exon	Exon 6 of 16	ENSP00000434391.1	Q86UD7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.27

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0040

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00061

LIST_S2

Benign

0.70

M_CAP

Benign

0.0024

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

PhyloP100

-0.29

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

REVEL

Benign

0.061

Sift

Benign

0.18

Sift4G

Uncertain

0.022

Polyphen

0.96

Vest4

0.17

MutPred

0.46

Gain of methylation at K77 (P = 0.0522)

MVP

0.099

MPC

0.89

ClinPred

0.41

GERP RS

-1.8

Varity_R

0.055

gMVP

0.030

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over