12-64836626-C-T

Variant names:

• chr12-64836626-C-T
• rs1046233473
• NM_015279.2:c.731C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015279.2(TBC1D30):​c.731C>T​(p.Thr244Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000684 in 1,535,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000069 (0 hom.)
• Consequence: TBC1D30 NM_015279.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.525
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02264154).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015279.2. 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
	TBC1D30	NM_015279.2	MANE Select	c.731C>T	p.Thr244Ile	missense	Exon 6 of 12	NP_056094.1	Q9Y2I9-2
	TBC1D30	NM_001330186.2		c.731C>T	p.Thr244Ile	missense	Exon 6 of 12	NP_001317115.1
	TBC1D30	NM_001330187.2		c.389C>T	p.Thr130Ile	missense	Exon 8 of 14	NP_001317116.1	F8VZ81

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D30	ENST00000539867.6	TSL:1 MANE Select	c.731C>T	p.Thr244Ile	missense	Exon 6 of 12	ENSP00000440207.1	Q9Y2I9-2
	TBC1D30	ENST00000542120.6	TSL:1	c.1220C>T	p.Thr407Ile	missense	Exon 7 of 13	ENSP00000440640.2	Q9Y2I9-1
	ENSG00000288591	ENST00000674281.1		n.389C>T		non_coding_transcript_exon	Exon 8 of 17	ENSP00000501395.1	F8VZ81

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152158 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000876 AC: 12 AN: 136956 AF XY: 0.0000671

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00105

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000694 AC: 96 AN: 1383614 Hom.: 0 Cov.: 30 AF XY: 0.0000703 AC XY: 48 AN XY: 682754

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00227 AC: 81 AN: 35720

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1078754

Other (OTH) AF: 0.0000346 AC: 2 AN: 57886

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152276 Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5 AN XY: 74446

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000378

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.077
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.53
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.013
Sift	Benign	0.14	T
Sift4G	Benign	0.19	T
Vest4		0.14
MVP		0.15
ClinPred		0.032	T
GERP RS		1.3
gMVP		0.29
Mutation Taster		=92/8	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: rs1046233473; hg19: chr12-65230406;