chr17-15741159-C-T

Variant names:

• chr17-15741159-C-T
• NM_001388465.1:c.584C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001388465.1(TBC1D26):​c.584C>T​(p.Ala195Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBC1D26 NM_001388465.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.649
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.584C>T	p.Ala195Val	missense	Exon 10 of 15	NP_001375394.1	A0A8J8ZQP4
	TBC1D26	NM_178571.4		c.584C>T	p.Ala195Val	missense	Exon 10 of 15	NP_848666.2	Q86UD7
	ZNF286A-TBC1D26	NR_171000.1		n.2773C>T		non_coding_transcript_exon	Exon 17 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D26	ENST00000437605.4	TSL:5 MANE Select	c.584C>T	p.Ala195Val	missense	Exon 10 of 15	ENSP00000410111.3	A0A8J8ZQP4
	ZNF286A-TBC1D26	ENST00000413242.6	TSL:2	n.*1348C>T		non_coding_transcript_exon	Exon 12 of 17	ENSP00000458062.1
	TBC1D26	ENST00000469477.3	TSL:1	n.584C>T		non_coding_transcript_exon	Exon 10 of 16	ENSP00000434391.1	Q86UD7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.014
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0072	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.65
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.75		Loss of catalytic residue at A195 (P = 0.1735)
MVP		0.57
MPC		0.47
ClinPred		0.96	D
GERP RS		0.71
Varity_R		0.69
gMVP		0.27

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

Other links and lift over

hg19: chr17-15644473;