12-64858338-A-G

Variant names:

• chr12-64858338-A-G
• rs939876
• NM_015279.2:c.1039-6330A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015279.2(TBC1D30):​c.1039-6330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,282 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.097 (886 hom., cov: 32)
• Consequence: TBC1D30 NM_015279.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D30	NM_015279.2	MANE Select	c.1039-6330A>G		intron	N/A	NP_056094.1
	TBC1D30	NM_001330186.2		c.1039-6330A>G		intron	N/A	NP_001317115.1
	TBC1D30	NM_001330187.2		c.697-6330A>G		intron	N/A	NP_001317116.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D30	ENST00000539867.6	TSL:1 MANE Select	c.1039-6330A>G		intron	N/A	ENSP00000440207.1
	TBC1D30	ENST00000542120.6	TSL:1	c.1528-6330A>G		intron	N/A	ENSP00000440640.2
	ENSG00000288591	ENST00000674281.1		n.697-6330A>G		intron	N/A	ENSP00000501395.1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14726 AN: 152164 Hom.: 887 Cov.: 32

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0970

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0967 AC: 14721 AN: 152282 Hom.: 886 Cov.: 32 AF XY: 0.0948 AC XY: 7056 AN XY: 74462

African (AFR) AF: 0.0330 AC: 1370 AN: 41562

American (AMR) AF: 0.0970 AC: 1484 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3468

East Asian (EAS) AF: 0.0379 AC: 196 AN: 5176

South Asian (SAS) AF: 0.0701 AC: 338 AN: 4824

European-Finnish (FIN) AF: 0.106 AC: 1129 AN: 10602

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9276 AN: 68024

Other (OTH) AF: 0.119 AC: 252 AN: 2114

Alfa AF: 0.123 Hom.: 5271

Bravo AF: 0.0938

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.49
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs939876; hg19: chr12-65252118;