rs1931757

chr10-94469409-C-T

Variant summary

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

The NM_015188.2(TBC1D12):c.1096-5259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 149,364 control chromosomes in the GnomAD database, including 35,620 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 0.69 (35620 hom., cov: 25)
• Consequence: TBC1D12 NM_015188.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.67

Genes affected

TBC1D12 (HGNC:29082): (TBC1 domain family member 12) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity; intracellular protein transport; and regulation of autophagosome assembly. Predicted to be active in autophagosome and recycling endosome. [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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D12	NM_015188.2	c.1096-5259C>T		intron_variant		ENST00000225235.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D12	ENST00000225235.5	c.1096-5259C>T		intron_variant		1	NM_015188.2	P1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 102337 AN: 149260 Hom.: 35606 Cov.: 25

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.784

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.686 AC: 102390 AN: 149364 Hom.: 35620 Cov.: 25 AF XY: 0.683 AC XY: 49624 AN XY: 72628

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.684

Alfa AF: 0.654 Hom.: 66273

Bravo AF: 0.688

Asia WGS AF: 0.761 AC: 2648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.30
Dann	Benign	0.45

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: rs1931757; hg19: chr10-96229166;