chr10-94402767-G-A

Variant names:

• chr10-94402767-G-A
• NM_015188.2:c.154G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015188.2(TBC1D12):​c.154G>A​(p.Ala52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D12 NM_015188.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.169
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06062901).

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.154G>A	p.Ala52Thr	missense	Exon 1 of 13	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.154G>A	p.Ala52Thr	missense	Exon 1 of 13	ENSP00000225235.4	O60347
	TBC1D12	ENST00000971288.1		c.154G>A	p.Ala52Thr	missense	Exon 1 of 12	ENSP00000641347.1
	TBC1D12	ENST00000904400.1		c.154G>A	p.Ala52Thr	missense	Exon 1 of 12	ENSP00000574459.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1381020 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 680908

African (AFR) AF: 0.00 AC: 0 AN: 31346

American (AMR) AF: 0.00 AC: 0 AN: 35616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24446

East Asian (EAS) AF: 0.00 AC: 0 AN: 35668

South Asian (SAS) AF: 0.00 AC: 0 AN: 79378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5046

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069234

Other (OTH) AF: 0.00 AC: 0 AN: 57254

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.17
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.042
Sift	Benign	0.14	T
Sift4G	Benign	0.32	T
Polyphen		0.030	B
Vest4		0.10
MutPred		0.11		Gain of phosphorylation at A52 (P = 0.0037)
MVP		0.17
MPC		0.47
ClinPred		0.12	T
PromoterAI		-0.031	Neutral
Varity_R		0.083
gMVP		0.025
Mutation Taster		=96/4	polymorphism

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

hg19: chr10-96162524;