10-94446347-T-G

Variant names:

• chr10-94446347-T-G
• rs11187952
• NM_015188.2:c.1095+4328T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015188.2(TBC1D12):​c.1095+4328T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,962 control chromosomes in the GnomAD database, including 15,629 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 0.45 (15629 hom., cov: 31)
• Consequence: TBC1D12 NM_015188.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015188.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D12	NM_015188.2	MANE Select	c.1095+4328T>G		intron	N/A	NP_056003.1	O60347

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D12	ENST00000225235.5	TSL:1 MANE Select	c.1095+4328T>G		intron	N/A	ENSP00000225235.4	O60347
	TBC1D12	ENST00000971288.1		c.1095+4328T>G		intron	N/A	ENSP00000641347.1
	TBC1D12	ENST00000904400.1		c.1095+4328T>G		intron	N/A	ENSP00000574459.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68056 AN: 151844 Hom.: 15630 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.448 AC: 68082 AN: 151962 Hom.: 15629 Cov.: 31 AF XY: 0.450 AC XY: 33439 AN XY: 74268

African (AFR) AF: 0.448 AC: 18561 AN: 41448

American (AMR) AF: 0.377 AC: 5761 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1409 AN: 3462

East Asian (EAS) AF: 0.793 AC: 4104 AN: 5174

South Asian (SAS) AF: 0.591 AC: 2845 AN: 4816

European-Finnish (FIN) AF: 0.402 AC: 4239 AN: 10552

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29745 AN: 67942

Other (OTH) AF: 0.436 AC: 914 AN: 2098

Alfa AF: 0.445 Hom.: 11380

Bravo AF: 0.445

Asia WGS AF: 0.675 AC: 2348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.70
PhyloP100		-0.77
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: rs11187952; hg19: chr10-96206104;