12-64759493-T-C

Position:

• chr12-64759493-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001330187.2(TBC1D30):​c.-532T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 501,868 control chromosomes in the GnomAD database, including 109,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (38333 hom., cov: 33)
  • Exomes 𝑓: 0.63 (71459 hom.)
• Consequence: TBC1D30 NM_001330187.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.73

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-64759493-T-C is Benign according to our data. Variant chr12-64759493-T-C is described in ClinVar as [Benign]. Clinvar id is 1269458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D30	NM_001330187.2	c.-532T>C		5_prime_UTR_variant	1/14		NP_001317116.1
TBC1D30	XM_047428595.1	c.-1895T>C		5_prime_UTR_variant	1/15		XP_047284551.1
TBC1D30	XM_047428596.1	c.-1895T>C		5_prime_UTR_variant	1/14		XP_047284552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D30	ENST00000674237.1	c.-532T>C		5_prime_UTR_variant	1/14			ENSP00000501371.1
ENSG00000288591	ENST00000674281.1	n.-532T>C		upstream_gene_variant				ENSP00000501395.1
TBC1D30	ENST00000434563.3	n.-28T>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105743 AN: 151956 Hom.: 38285 Cov.: 33

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.629 AC: 220189 AN: 349794 Hom.: 71459 Cov.: 2 AF XY: 0.628 AC XY: 114379 AN XY: 182004

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.519

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.660

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.594

Gnomad4 OTH exome AF: 0.628

GnomAD4 genome AF: 0.696 AC: 105842 AN: 152074 Hom.: 38333 Cov.: 33 AF XY: 0.696 AC XY: 51755 AN XY: 74326

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.668

Alfa AF: 0.655 Hom.: 4193

Bravo AF: 0.701

Asia WGS AF: 0.771 AC: 2665 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1147090; hg19: chr12-65153273;