12-64832208-C-T

Variant names:

• chr12-64832208-C-T
• rs181148724
• NM_015279.2:c.498C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_015279.2(TBC1D30):​c.498C>T​(p.Ala166Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00653 in 1,536,098 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (43 hom.)
• Consequence: TBC1D30 NM_015279.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72
• Publications: 0 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 12-64832208-C-T is Benign according to our data. Variant chr12-64832208-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.72 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.498C>T	p.Ala166Ala	synonymous	Exon 5 of 12	NP_056094.1	Q9Y2I9-2
	TBC1D30	NM_001330186.2		c.498C>T	p.Ala166Ala	synonymous	Exon 5 of 12	NP_001317115.1
	TBC1D30	NM_001330187.2		c.156C>T	p.Ala52Ala	synonymous	Exon 7 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.498C>T	p.Ala166Ala	synonymous	Exon 5 of 12	ENSP00000440207.1	Q9Y2I9-2
	TBC1D30	ENST00000542120.6	TSL:1	c.987C>T	p.Ala329Ala	synonymous	Exon 6 of 13	ENSP00000440640.2	Q9Y2I9-1
	ENSG00000288591	ENST00000674281.1		n.156C>T		non_coding_transcript_exon	Exon 7 of 17	ENSP00000501395.1	F8VZ81

Frequencies

GnomAD3 genomes AF: 0.00552 AC: 840 AN: 152168 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00989

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00833

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00491 AC: 673 AN: 137072 AF XY: 0.00440

Gnomad AFR exome AF: 0.000155

Gnomad AMR exome AF: 0.00315

Gnomad ASJ exome AF: 0.0104

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0138

Gnomad NFE exome AF: 0.00732

Gnomad OTH exome AF: 0.00476

GnomAD4 exome AF: 0.00665 AC: 9196 AN: 1383812 Hom.: 43 Cov.: 31 AF XY: 0.00658 AC XY: 4495 AN XY: 682846

African (AFR) AF: 0.000950 AC: 30 AN: 31594

American (AMR) AF: 0.00314 AC: 112 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00973 AC: 245 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35734

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79236

European-Finnish (FIN) AF: 0.0130 AC: 439 AN: 33890

Middle Eastern (MID) AF: 0.000702 AC: 4 AN: 5696

European-Non Finnish (NFE) AF: 0.00743 AC: 8018 AN: 1078876

Other (OTH) AF: 0.00598 AC: 346 AN: 57906

GnomAD4 genome AF: 0.00552 AC: 840 AN: 152286 Hom.: 5 Cov.: 33 AF XY: 0.00545 AC XY: 406 AN XY: 74446

African (AFR) AF: 0.000914 AC: 38 AN: 41560

American (AMR) AF: 0.00412 AC: 63 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00989 AC: 105 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00833 AC: 567 AN: 68028

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00634 Hom.: 1

Bravo AF: 0.00482

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	9.2
DANN	Benign	0.67
PhyloP100		1.7
Mutation Taster		=99/1	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: rs181148724; hg19: chr12-65225988;