3-17417089-G-C

Variant names:

• chr3-17417089-G-C
• rs6792747
• NM_001349074.2:c.168-10563C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349074.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D5	NM_001349074.2	MANE Select	c.168-10563C>G		intron	N/A	NP_001336003.1
	TBC1D5	NM_001134381.2		c.168-10563C>G		intron	N/A	NP_001127853.1
	TBC1D5	NM_001349073.2		c.168-10563C>G		intron	N/A	NP_001336002.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D5	ENST00000696125.1	MANE Select	c.168-10563C>G		intron	N/A	ENSP00000512418.1
	TBC1D5	ENST00000446818.6	TSL:1	c.168-10563C>G		intron	N/A	ENSP00000402935.2
	TBC1D5	ENST00000253692.11	TSL:1	c.168-10563C>G		intron	N/A	ENSP00000253692.6

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

African (AFR) AF: 0.255 AC: 10572 AN: 41426

American (AMR) AF: 0.0431 AC: 659 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00808 AC: 28 AN: 3466

East Asian (EAS) AF: 0.0444 AC: 230 AN: 5180

South Asian (SAS) AF: 0.0670 AC: 323 AN: 4824

European-Finnish (FIN) AF: 0.0656 AC: 695 AN: 10592

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0175 AC: 1191 AN: 68004

Other (OTH) AF: 0.0650 AC: 137 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.50
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs6792747; hg19: chr3-17458581;