rs761302886

Variant names:

• chr10-94402971-G-A
• rs761302886
• NM_015188.2:c.358G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-94402971-G-A
• chr10-94402971-G-C
• chr10-94402971-G-T

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.358G>A​(p.Ala120Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000425 in 1,575,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: TBC1D12 NM_015188.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.468
• 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=0.05335623).

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.358G>A	p.Ala120Thr	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.358G>A	p.Ala120Thr	missense	Exon 1 of 13	ENSP00000225235.4	O60347
	TBC1D12	ENST00000971288.1		c.358G>A	p.Ala120Thr	missense	Exon 1 of 12	ENSP00000641347.1
	TBC1D12	ENST00000904400.1		c.358G>A	p.Ala120Thr	missense	Exon 1 of 12	ENSP00000574459.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152006 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000432 AC: 8 AN: 185214 AF XY: 0.0000575

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000393 AC: 56 AN: 1423214 Hom.: 0 Cov.: 30 AF XY: 0.0000368 AC XY: 26 AN XY: 707186

African (AFR) AF: 0.00 AC: 0 AN: 29310

American (AMR) AF: 0.0000736 AC: 3 AN: 40748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24866

East Asian (EAS) AF: 0.00 AC: 0 AN: 35220

South Asian (SAS) AF: 0.00 AC: 0 AN: 81962

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.0000446 AC: 49 AN: 1097482

Other (OTH) AF: 0.0000511 AC: 3 AN: 58692

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152114 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41530

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67938

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000299 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000264 AC: 3

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	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.47
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.014
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.15	T
Polyphen		0.029	B
Vest4		0.022
MutPred		0.12		Gain of phosphorylation at A120 (P = 0.016)
MVP		0.21
MPC		0.48
ClinPred		0.048	T
GERP RS		-1.3
PromoterAI		-0.0084	Neutral
Varity_R		0.048
gMVP		0.063
Mutation Taster		=100/0	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

dbSNP: rs761302886; hg19: chr10-96162728;