rs939876

Positions:

• chr12-64858338-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D30	NM_015279.2	c.1039-6330A>G		intron_variant		ENST00000539867.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D30	ENST00000539867.6	c.1039-6330A>G		intron_variant		1	NM_015279.2	P1
TBC1D30	ENST00000542120.6	c.1528-6330A>G		intron_variant		1
TBC1D30	ENST00000674237.1	c.697-6330A>G		intron_variant
TBC1D30	ENST00000674171.1	c.*878-6330A>G		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0379

Gnomad4 SAS AF: 0.0701

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.119

Alfa AF: 0.129 Hom.: 2654

Bravo AF: 0.0938

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs939876; hg19: chr12-65252118;