Variant 4-146820225-A-T 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.1001T>A(p.Ile334Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,204 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TTC29
NM_031956.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48

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:

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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.1001T>A	p.Ile334Asn	missense_variant	10/13	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.1001T>A	p.Ile334Asn	missense_variant	10/13	1	NM_031956.4	ENSP00000316740	P4	Q8NA56-1
TTC29	ENST00000508306.5 linkuse as main transcript	c.*63T>A		3_prime_UTR_variant, NMD_transcript_variant	11/14	1		ENSP00000422648
TTC29	ENST00000513335.5 linkuse as main transcript	c.1079T>A	p.Ile360Asn	missense_variant	11/14	2		ENSP00000423505
TTC29	ENST00000504425.5 linkuse as main transcript	c.1001T>A	p.Ile334Asn	missense_variant	10/13	5		ENSP00000425778	A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000485

AC:

AN:

247436

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

134342

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000671

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:

0.00000479

AC:

AN:

1460204

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726430

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

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.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000331

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

May 09, 2023

The c.1001T>A (p.I334N) alteration is located in exon 10 (coding exon 8) of the TTC29 gene. This alteration results from a T to A substitution at nucleotide position 1001, causing the isoleucine (I) at amino acid position 334 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

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

.;T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.81

T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Uncertain

0.53

MutationAssessor

Uncertain

2.6

.;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.1

D;D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.69

MutPred

0.55

Gain of disorder (P = 0.019);.;.;

MVP

0.84

MPC

0.11

ClinPred

0.65

GERP RS

5.9

Varity_R

0.84

gMVP

0.58

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