10-94515282-C-T

Position:

• chr10-94515282-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.1761+3628C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,818 control chromosomes in the GnomAD database, including 2,171 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 0.16 (2171 hom., cov: 31)
• Consequence: TBC1D12 NM_015188.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D12	NM_015188.2	c.1761+3628C>T		intron_variant		ENST00000225235.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D12	ENST00000225235.5	c.1761+3628C>T		intron_variant		1	NM_015188.2	P1
TBC1D12	ENST00000485048.1	n.1810+3628C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23630 AN: 151700 Hom.: 2174 Cov.: 31

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.156 AC: 23615 AN: 151818 Hom.: 2171 Cov.: 31 AF XY: 0.156 AC XY: 11551 AN XY: 74186

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.175

Alfa AF: 0.179 Hom.: 1209

Bravo AF: 0.159

Asia WGS AF: 0.262 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.5
DANN	Benign	0.58

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: rs12220941; hg19: chr10-96275039;