Variant 4-146867532-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_031956.4(TTC29):c.851A>G(p.His284Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000224 in 1,554,688 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

TTC29
NM_031956.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 5.69

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 Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22488242).

BP6

Variant 4-146867532-T-C is Benign according to our data. Variant chr4-146867532-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2655113.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC29	NM_031956.4 linkuse as main transcript	c.851A>G	p.His284Arg	missense_variant	8/13	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.851A>G	p.His284Arg	missense_variant	8/13	1	NM_031956.4	ENSP00000316740	P4	Q8NA56-1
TTC29	ENST00000508306.5 linkuse as main transcript	c.851A>G	p.His284Arg	missense_variant, NMD_transcript_variant	8/14	1		ENSP00000422648
TTC29	ENST00000513335.5 linkuse as main transcript	c.929A>G	p.His310Arg	missense_variant	9/14	2		ENSP00000423505
TTC29	ENST00000504425.5 linkuse as main transcript	c.851A>G	p.His284Arg	missense_variant	8/13	5		ENSP00000425778	A1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000199

AC:

AN:

195712

Hom.:

AF XY:

0.000171

AC XY:

AN XY:

105468

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00158

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000170

Gnomad FIN exome

AF:

0.000155

Gnomad NFE exome

AF:

0.000198

Gnomad OTH exome

AF:

0.000210

GnomAD4 exome

AF:

0.000226

AC:

317

AN:

1402390

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

169

AN XY:

694480

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000523

Gnomad4 ASJ exome

AF:

0.00129

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.000296

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.000208

GnomAD4 genome

AF:

0.000204

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000629

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.000192

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.851A>G (p.H284R) alteration is located in exon 8 (coding exon 6) of the TTC29 gene. This alteration results from a A to G substitution at nucleotide position 851, causing the histidine (H) at amino acid position 284 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

TTC29: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

.;T;.;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.6

.;M;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-4.3

D;D;.;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.024

D;D;.;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.96

D;D;.;D

Vest4

0.40

MVP

0.77

MPC

0.036

ClinPred

0.41

GERP RS

5.5

Varity_R

0.37

gMVP

0.48

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