rs6792747

Positions:

• chr3-17417089-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349074.2(TBC1D5):​c.168-10563C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 152,092 control chromosomes in the GnomAD database, including 1,423 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.091 (1423 hom., cov: 32)
• Consequence: TBC1D5 NM_001349074.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

Genes affected

TBC1D5 (HGNC:19166): (TBC1 domain family member 5) Enables AP-2 adaptor complex binding activity and retromer complex binding activity. Involved in several processes, including macroautophagy; positive regulation of receptor internalization; and retrograde transport, endosome to Golgi. Located in Golgi apparatus; autophagosome; and endosome membrane. Part of retromer complex. Colocalizes with AP-2 adaptor complex and Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D5	NM_001349074.2	c.168-10563C>G		intron_variant		ENST00000696125.1	NP_001336003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D5	ENST00000696125.1	c.168-10563C>G		intron_variant			NM_001349074.2	ENSP00000512418	P2

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13781 AN: 151976 Hom.: 1405 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.0441

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0638

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0910 AC: 13845 AN: 152092 Hom.: 1423 Cov.: 32 AF XY: 0.0915 AC XY: 6805 AN XY: 74344

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.00808

Gnomad4 EAS AF: 0.0444

Gnomad4 SAS AF: 0.0670

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0650

Alfa AF: 0.0665 Hom.: 127

Bravo AF: 0.0963

Asia WGS AF: 0.0740 AC: 256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs6792747; hg19: chr3-17458581;