17-15740129-C-T

Variant names:

• chr17-15740129-C-T
• rs758806406
• NM_001388465.1:c.527C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001388465.1(TBC1D26):​c.527C>T​(p.Ala176Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A176D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: TBC1D26 NM_001388465.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D26	NM_001388465.1	MANE Select	c.527C>T	p.Ala176Val	missense	Exon 9 of 15	NP_001375394.1	A0A8J8ZQP4
	TBC1D26	NM_178571.4		c.527C>T	p.Ala176Val	missense	Exon 9 of 15	NP_848666.2	Q86UD7
	ZNF286A-TBC1D26	NR_171000.1		n.2716C>T		non_coding_transcript_exon	Exon 16 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D26	ENST00000437605.4	TSL:5 MANE Select	c.527C>T	p.Ala176Val	missense	Exon 9 of 15	ENSP00000410111.3	A0A8J8ZQP4
	ZNF286A-TBC1D26	ENST00000413242.6	TSL:2	n.*1291C>T		non_coding_transcript_exon	Exon 11 of 17	ENSP00000458062.1
	TBC1D26	ENST00000469477.3	TSL:1	n.527C>T		non_coding_transcript_exon	Exon 9 of 16	ENSP00000434391.1	Q86UD7-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152160 Hom.: 0 Cov.: 33

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 249504 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000315 AC: 46 AN: 1461814 Hom.: 0 Cov.: 34 AF XY: 0.0000303 AC XY: 22 AN XY: 727204

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152160 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000331 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.010
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0028	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.3
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.79		Loss of catalytic residue at A176 (P = 0.2355)
MVP		0.48
MPC		0.63
ClinPred		0.92	D
GERP RS		1.5
Varity_R		0.81
gMVP		0.42
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs758806406; hg19: chr17-15643443;