chr17-15738326-G-A

Position:

chr17-15738326-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001388465.1(TBC1D26):c.326G>A(p.Arg109Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000366 in 1,613,710 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

TBC1D26
NM_001388465.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.537

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 (HGNC:):

TBC1D26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011331409).

BP6

Variant 17-15738326-G-A is Benign according to our data. Variant chr17-15738326-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2520609.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D26	NM_001388465.1 linkuse as main transcript	c.326G>A	p.Arg109Gln	missense_variant	7/15	ENST00000437605.4	NP_001375394.1
TBC1D26	NM_178571.4 linkuse as main transcript	c.326G>A	p.Arg109Gln	missense_variant	7/15		NP_848666.2	Q86UD7
ZNF286A-TBC1D26	NR_171000.1 linkuse as main transcript	n.2515G>A		non_coding_transcript_exon_variant	14/23
TBC1D26-AS1	XR_001753084.3 linkuse as main transcript	n.150-1777C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBC1D26	ENST00000437605.4 linkuse as main transcript	c.326G>A	p.Arg109Gln	missense_variant	7/15	5	NM_001388465.1	ENSP00000410111.3	A0A8J8ZQP4
ZNF286A-TBC1D26	ENST00000413242.6 linkuse as main transcript	n.*1090G>A		non_coding_transcript_exon_variant	9/17	2		ENSP00000458062.1
ZNF286A-TBC1D26	ENST00000413242.6 linkuse as main transcript	n.*1090G>A		3_prime_UTR_variant	9/17	2		ENSP00000458062.1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000305

AC:

AN:

249378

Hom.:

AF XY:

0.000325

AC XY:

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000538

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000382

AC:

558

AN:

1461540

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

282

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.000457

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000217

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000403

Hom.:

Bravo

AF:

0.000223

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000970

AC:

ExAC

AF:

0.000339

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3464

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.089

DANN

Benign

0.48

DEOGEN2

Benign

0.0011

.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.46

T;T;.

M_CAP

Benign

0.0020

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.26

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

1.6

.;N;.

REVEL

Benign

0.038

Sift

Benign

0.79

.;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.014

B;B;B

Vest4

0.18

MVP

0.048

MPC

0.80

ClinPred

0.015

GERP RS

-2.9

Varity_R

0.022

gMVP

0.061

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

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