12-64836589-A-G

Position:

• chr12-64836589-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015279.2(TBC1D30):​c.694A>G​(p.Arg232Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TBC1D30 NM_015279.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43

Genes affected

TBC1D30 (HGNC:29164): (TBC1 domain family member 30) Enables GTPase activator activity and small GTPase binding activity. Involved in negative regulation of cilium assembly and positive regulation of GTPase activity. Located in ciliary basal body; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288591 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D30	NM_015279.2	c.694A>G	p.Arg232Gly	missense_variant	6/12	ENST00000539867.6	NP_056094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D30	ENST00000539867.6	c.694A>G	p.Arg232Gly	missense_variant	6/12	1	NM_015279.2	ENSP00000440207.1
ENSG00000288591	ENST00000674281.1	n.352A>G		non_coding_transcript_exon_variant	8/17			ENSP00000501395.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383744 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 682816

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2022

The c.694A>G (p.R232G) alteration is located in exon 6 (coding exon 6) of the TBC1D30 gene. This alteration results from a A to G substitution at nucleotide position 694, causing the arginine (R) at amino acid position 232 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Uncertain	0.35
Sift	Benign	0.057	T;D
Sift4G	Uncertain	0.0080	D;D
Vest4		0.83
MVP		0.45
ClinPred		0.98	D
GERP RS		4.0
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-65230369;