Variant 12-64870677-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000539867.6(TBC1D30):c.1367G>A(p.Ser456Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000217 in 1,383,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

TBC1D30
ENST00000539867.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Variant links:

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]

TBC1D30 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22402096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D30	NM_015279.2 linkuse as main transcript	c.1367G>A	p.Ser456Asn	missense_variant	11/12	ENST00000539867.6	NP_056094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D30	ENST00000539867.6 linkuse as main transcript	c.1367G>A	p.Ser456Asn	missense_variant	11/12	1	NM_015279.2	ENSP00000440207	P1	Q9Y2I9-2
TBC1D30	ENST00000542120.6 linkuse as main transcript	c.1856G>A	p.Ser619Asn	missense_variant	12/13	1		ENSP00000440640		Q9Y2I9-1
TBC1D30	ENST00000674237.1 linkuse as main transcript	c.1025G>A	p.Ser342Asn	missense_variant	13/14			ENSP00000501371
TBC1D30	ENST00000674171.1 linkuse as main transcript	c.*1206G>A		3_prime_UTR_variant, NMD_transcript_variant	12/13			ENSP00000501420

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000145

AC:

AN:

137654

Hom.:

AF XY:

0.0000268

AC XY:

AN XY:

74688

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000190

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1383856

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

682872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.1367G>A (p.S456N) alteration is located in exon 11 (coding exon 11) of the TBC1D30 gene. This alteration results from a G to A substitution at nucleotide position 1367, causing the serine (S) at amino acid position 456 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.63

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.14

Sift

Benign

0.035

D;D

Sift4G

Uncertain

0.046

D;D

Vest4

0.20

MVP

0.26

ClinPred

0.27

GERP RS

5.9

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over