Variant 4-146833843-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_031956.4(TTC29):c.940G>A(p.Gly314Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 1,613,290 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 21 hom. )

Consequence

TTC29
NM_031956.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

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:

LOC105377474 (HGNC:):

LOC105377474 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013542175).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00286 (435/152262) while in subpopulation NFE AF= 0.00469 (319/68030). AF 95% confidence interval is 0.00427. There are 2 homozygotes in gnomad4. There are 209 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC29	NM_031956.4 linkuse as main transcript	c.940G>A	p.Gly314Arg	missense_variant	9/13	ENST00000325106.9
LOC105377474	XR_939314.2 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC29	ENST00000325106.9 linkuse as main transcript	c.940G>A	p.Gly314Arg	missense_variant	9/13	1	NM_031956.4	P4	Q8NA56-1
TTC29	ENST00000508306.5 linkuse as main transcript	c.940G>A	p.Gly314Arg	missense_variant, NMD_transcript_variant	9/14	1
TTC29	ENST00000513335.5 linkuse as main transcript	c.1018G>A	p.Gly340Arg	missense_variant	10/14	2
TTC29	ENST00000504425.5 linkuse as main transcript	c.940G>A	p.Gly314Arg	missense_variant	9/13	5		A1

Frequencies

GnomAD3 genomes

AF:

0.00286

AC:

435

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00528

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00469

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00260

AC:

646

AN:

248264

Hom.:

AF XY:

0.00245

AC XY:

330

AN XY:

134670

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.000697

Gnomad ASJ exome

AF:

0.000797

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000850

Gnomad FIN exome

AF:

0.00414

Gnomad NFE exome

AF:

0.00429

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00431

AC:

6298

AN:

1461028

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

3056

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.00379

Gnomad4 NFE exome

AF:

0.00519

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00286

AC:

435

AN:

152262

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00528

Gnomad4 NFE

AF:

0.00469

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00394

Hom.:

Bravo

AF:

0.00242

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000772

AC:

ESP6500EA

AF:

0.00386

AC:

ExAC

AF:

0.00236

AC:

285

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00409

EpiControl

AF:

0.00314

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.53

MutationTaster

Benign

0.92

D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Uncertain

0.61

Sift

Benign

0.054

T;D;D

Sift4G

Benign

0.38

T;T;T

Polyphen

0.83

P;D;D

Vest4

0.67

MutPred

0.67

Loss of methylation at R341 (P = 0.0455);.;.;

MVP

0.75

MPC

0.086

ClinPred

0.026

GERP RS

3.9

Varity_R

0.54

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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