NM_001388465.1:c.244C>T

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

1
18

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

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
TBC1D26NM_001388465.1 linkc.244C>T p.Leu82Phe missense_variant Exon 6 of 15 ENST00000437605.4 NP_001375394.1
TBC1D26NM_178571.4 linkc.244C>T p.Leu82Phe missense_variant Exon 6 of 15 NP_848666.2 Q86UD7
ZNF286A-TBC1D26NR_171000.1 linkn.2433C>T non_coding_transcript_exon_variant Exon 13 of 23
TBC1D26-AS1XR_001753084.3 linkn.150-1493G>A intron_variant Intron 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBC1D26ENST00000437605.4 linkc.244C>T p.Leu82Phe missense_variant Exon 6 of 15 5 NM_001388465.1 ENSP00000410111.3 A0A8J8ZQP4
ZNF286A-TBC1D26ENST00000413242.6 linkn.*806C>T non_coding_transcript_exon_variant Exon 9 of 17 2 ENSP00000458062.1
ZNF286A-TBC1D26ENST00000413242.6 linkn.*806C>T 3_prime_UTR_variant Exon 9 of 17 2 ENSP00000458062.1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
32
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:
5
AN:
1461876
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
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:
1
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
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
T
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
N
LIST_S2
Benign
0.62
T;T;.
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.071
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.4
L;L;L
PrimateAI
Benign
0.44
T
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
T
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.

Other links and lift over

dbSNP: rs1383446153; hg19: chr17-15641356; API