Variant 2-19897018-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001008237.3(TTC32):c.425A>G(p.Lys142Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000823 in 1,591,300 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

TTC32
NM_001008237.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56

Variant links:

Genes affected

TTC32 (HGNC:32954): (tetratricopeptide repeat domain 32)

TTC32 links:

TTC32 (HGNC:):

TTC32 links:

Genome browser will be placed here

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=0.14757466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC32	NM_001008237.3 linkuse as main transcript	c.425A>G	p.Lys142Arg	missense_variant	3/3	ENST00000333610.4	NP_001008238.1	Q5I0X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTC32	ENST00000333610.4 linkuse as main transcript	c.425A>G	p.Lys142Arg	missense_variant	3/3	1	NM_001008237.3	ENSP00000333018.3	Q5I0X7
TTC32	ENST00000402414.1 linkuse as main transcript	c.*99A>G		3_prime_UTR_variant	2/2	5		ENSP00000385708.1	B5MCJ1
TTC32	ENST00000495698.1 linkuse as main transcript	n.*8A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000475

AC:

AN:

231444

Hom.:

AF XY:

0.0000398

AC XY:

AN XY:

125634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000876

AC:

126

AN:

1438990

Hom.:

Cov.:

AF XY:

0.0000783

AC XY:

AN XY:

715526

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:

0.000112

Gnomad4 OTH exome

AF:

0.0000505

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

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

Oct 01, 2024

The c.425A>G (p.K142R) alteration is located in exon 3 (coding exon 3) of the TTC32 gene. This alteration results from a A to G substitution at nucleotide position 425, causing the lysine (K) at amino acid position 142 to be replaced by an arginine (R). 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

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

M_CAP

Benign

0.010

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.2

REVEL

Benign

0.11

Sift

Benign

0.13

Sift4G

Benign

0.17

Polyphen

0.20

Vest4

0.49

MVP

0.43

MPC

0.046

ClinPred

0.26

GERP RS

5.6

Varity_R

0.23

gMVP

0.46

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

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