dbSNP rs766449743: TBC1D26:p.Pro58Ser (chr17-15737497-C-T) – 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.172C>T(p.Pro58Ser) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TBC1D26
NM_001388465.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.480

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=0.14298615).

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.172C>T	p.Pro58Ser	missense	Exon 5 of 15	NP_001375394.1	A0A8J8ZQP4
TBC1D26	NM_178571.4		c.172C>T	p.Pro58Ser	missense	Exon 5 of 15	NP_848666.2	Q86UD7
ZNF286A-TBC1D26	NR_171000.1		n.2361C>T		non_coding_transcript_exon	Exon 12 of 23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D26	ENST00000437605.4	TSL:5 MANE Select	c.172C>T	p.Pro58Ser	missense	Exon 5 of 15	ENSP00000410111.3	A0A8J8ZQP4
ZNF286A-TBC1D26	ENST00000413242.6	TSL:2	n.*261C>T		non_coding_transcript_exon	Exon 9 of 17	ENSP00000458062.1
TBC1D26	ENST00000469477.3	TSL:1	n.172C>T		non_coding_transcript_exon	Exon 5 of 16	ENSP00000434391.1	Q86UD7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000325

AC:

AN:

184874

AF XY:

0.0000100

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000401

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1147514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

576798

African (AFR)

AF:

0.00

AC:

AN:

25254

American (AMR)

AF:

0.00

AC:

AN:

33696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21306

East Asian (EAS)

AF:

0.00

AC:

AN:

37256

South Asian (SAS)

AF:

0.00

AC:

AN:

74612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3808

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

851888

Other (OTH)

AF:

0.00

AC:

AN:

49450

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000283

AC:

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

0.15

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.65

M_CAP

Benign

0.0026

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

0.48

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.073

Sift

Uncertain

0.0010

Sift4G

Benign

0.12

Polyphen

0.86

Vest4

0.25

MutPred

0.38

Loss of loop (P = 0.0512)

MVP

0.25

MPC

0.70

ClinPred

0.56

GERP RS

0.89

Varity_R

0.17

gMVP

0.12

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over