Variant 4-146903579-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031956.4(TTC29):c.551C>T(p.Ala184Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,611,960 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TTC29
NM_031956.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

TTC29 (HGNC:29936): (tetratricopeptide repeat domain 29) Involved in cilium movement and cilium organization. Located in sperm flagellum. Implicated in spermatogenic failure 42. [provided by Alliance of Genome Resources, Apr 2022]

TTC29 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC29	NM_031956.4 linkuse as main transcript	c.551C>T	p.Ala184Val	missense_variant	6/13	ENST00000325106.9	NP_114162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC29	ENST00000325106.9 linkuse as main transcript	c.551C>T	p.Ala184Val	missense_variant	6/13	1	NM_031956.4	ENSP00000316740	P4	Q8NA56-1
TTC29	ENST00000508306.5 linkuse as main transcript	c.551C>T	p.Ala184Val	missense_variant, NMD_transcript_variant	6/14	1		ENSP00000422648
TTC29	ENST00000513335.5 linkuse as main transcript	c.629C>T	p.Ala210Val	missense_variant	7/14	2		ENSP00000423505
TTC29	ENST00000504425.5 linkuse as main transcript	c.551C>T	p.Ala184Val	missense_variant	6/13	5		ENSP00000425778	A1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000324

AC:

AN:

246676

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

133896

show subpopulations

Gnomad AFR exome

AF:

0.000522

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1459826

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726190

show subpopulations

Gnomad4 AFR exome

AF:

0.000570

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:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000145

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000531

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000414

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

Jun 16, 2022

The c.551C>T (p.A184V) alteration is located in exon 6 (coding exon 4) of the TTC29 gene. This alteration results from a C to T substitution at nucleotide position 551, causing the alanine (A) at amino acid position 184 to be replaced by a valine (V). 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

0.26

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.047

.;T;.;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.62

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;M;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.0

D;D;.;D

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;D;.;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.71

MVP

0.45

MPC

0.11

ClinPred

0.69

GERP RS

5.6

Varity_R

0.28

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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