NM_001388465.1:c.244C>T

Variant names:

• chr17-15738042-C-T
• rs1383446153
• NM_001388465.1:c.244C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_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. 16/22 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.295
• 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: Likely_benign. The variant received -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 VariationId is 3453475.Status of the report is criteria_provided_single_submitter, 1 stars.

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.244C>T	p.Leu82Phe	missense	Exon 6 of 15	NP_001375394.1	A0A8J8ZQP4
	TBC1D26	NM_178571.4		c.244C>T	p.Leu82Phe	missense	Exon 6 of 15	NP_848666.2	Q86UD7
	ZNF286A-TBC1D26	NR_171000.1		n.2433C>T		non_coding_transcript_exon	Exon 13 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D26	ENST00000437605.4	TSL:5 MANE Select	c.244C>T	p.Leu82Phe	missense	Exon 6 of 15	ENSP00000410111.3	A0A8J8ZQP4
	ZNF286A-TBC1D26	ENST00000413242.6	TSL:2	n.*806C>T		non_coding_transcript_exon	Exon 9 of 17	ENSP00000458062.1
	TBC1D26	ENST00000469477.3	TSL:1	n.244C>T		non_coding_transcript_exon	Exon 6 of 16	ENSP00000434391.1	Q86UD7-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32

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

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112008

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.22
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
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.29
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.026
Sift	Benign	0.077	T
Sift4G	Benign	0.24	T
Polyphen		0.28	B
Vest4		0.095
MutPred		0.49		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
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: rs1383446153; hg19: chr17-15641356;