rs2337387

Positions:

• chr3-17832158-G-A
• chr3-17832158-G-C
• chr3-17832158-G-T

Variant summary

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

The ENST00000414318.2(TBC1D5):​n.212-524024C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,892 control chromosomes in the GnomAD database, including 21,534 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 0.52 (21534 hom., cov: 31)
• Consequence: TBC1D5 ENST00000414318.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D5	ENST00000414318.2	n.212-524024C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79132 AN: 151776 Hom.: 21510 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.521 AC: 79208 AN: 151892 Hom.: 21534 Cov.: 31 AF XY: 0.530 AC XY: 39363 AN XY: 74224

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.505

Alfa AF: 0.505 Hom.: 4112

Bravo AF: 0.521

Asia WGS AF: 0.770 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.69
DANN	Benign	0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2337387; hg19: chr3-17873650;