NM_001388465.1:c.244C>T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001388465.1(TBC1D26):c.244C>T(p.Leu82Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,064 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TBC1D26
NM_001388465.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.295

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07113919).

BP6

Variant 17-15738042-C-T is Benign according to our data. Variant chr17-15738042-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3453475.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D26	NM_001388465.1 link	c.244C>T	p.Leu82Phe	missense_variant	Exon 6 of 15	ENST00000437605.4	NP_001375394.1
TBC1D26	NM_178571.4 link	c.244C>T	p.Leu82Phe	missense_variant	Exon 6 of 15		NP_848666.2	Q86UD7
ZNF286A-TBC1D26	NR_171000.1 link	n.2433C>T		non_coding_transcript_exon_variant	Exon 13 of 23
TBC1D26-AS1	XR_001753084.3 link	n.150-1493G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBC1D26	ENST00000437605.4 link	c.244C>T	p.Leu82Phe	missense_variant	Exon 6 of 15	5	NM_001388465.1	ENSP00000410111.3	A0A8J8ZQP4
ZNF286A-TBC1D26	ENST00000413242.6 link	n.*806C>T		non_coding_transcript_exon_variant	Exon 9 of 17	2		ENSP00000458062.1
ZNF286A-TBC1D26	ENST00000413242.6 link	n.*806C>T		3_prime_UTR_variant	Exon 9 of 17	2		ENSP00000458062.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

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:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 22, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

0.22

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.38

DANN

Benign

0.67

DEOGEN2

Benign

0.038

.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00053

LIST_S2

Benign

0.62

T;T;.

M_CAP

Benign

0.0042

MetaRNN

Benign

0.071

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;L;L

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.9

.;D;.

REVEL

Benign

0.026

Sift

Benign

0.077

.;T;.

Sift4G

Benign

0.24

T;T;T

Polyphen

0.28

B;B;B

Vest4

0.095

MutPred

0.49

Gain of methylation at K77 (P = 0.0665);Gain of methylation at K77 (P = 0.0665);Gain of methylation at K77 (P = 0.0665);

MVP

0.061

MPC

0.76

ClinPred

0.14

GERP RS

-1.8

Varity_R

0.084

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