Variant 6-121106064-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152730.6(TBC1D32):c.3424G>A(p.Val1142Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TBC1D32
NM_152730.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.53

Variant links:

Genes affected

TBC1D32 (HGNC:21485): (TBC1 domain family member 32) This gene encodes a TBC-domain containing protein. Studies of a similar protein in mouse and zebrafish suggest that the encoded protein is involved in sonic hedgehog signaling, and that it interacts with and stabilizes cell cycle-related kinase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TBC1D32 links:

TBC1D32 (HGNC:):

TBC1D32 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D32	NM_152730.6 linkuse as main transcript	c.3424G>A	p.Val1142Met	missense_variant	30/32	ENST00000398212.7	NP_689943.4	Q96NH3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBC1D32	ENST00000398212.7 linkuse as main transcript	c.3424G>A	p.Val1142Met	missense_variant	30/32	5	NM_152730.6	ENSP00000381270.2	Q96NH3-1
TBC1D32	ENST00000275159.11 linkuse as main transcript	c.3547G>A	p.Val1183Met	missense_variant	31/33	5		ENSP00000275159.6	Q96NH3-4
TBC1D32	ENST00000464622.5 linkuse as main transcript	n.*4064G>A		non_coding_transcript_exon_variant	34/36	2		ENSP00000428839.1	Q96NH3-5
TBC1D32	ENST00000464622.5 linkuse as main transcript	n.*4064G>A		3_prime_UTR_variant	34/36	2		ENSP00000428839.1	Q96NH3-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456566

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724600

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

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

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.3424G>A (p.V1142M) alteration is located in exon 30 (coding exon 30) of the TBC1D32 gene. This alteration results from a G to A substitution at nucleotide position 3424, causing the valine (V) at amino acid position 1142 to be replaced by a methionine (M). 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

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

.;M

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

.;D

Vest4

0.90

MutPred

0.35

.;Gain of helix (P = 0.0199);

MVP

0.67

MPC

0.28

ClinPred

0.96

GERP RS

5.1

Varity_R

0.41

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over