4-146803630-T-G

Variant summary

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

The NM_031956.4(TTC29):ā€‹c.1157A>Cā€‹(p.Glu386Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

TTC29
NM_031956.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07
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]

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=0.16001719).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TTC29NM_031956.4 linkuse as main transcriptc.1157A>C p.Glu386Ala missense_variant 11/13 ENST00000325106.9 NP_114162.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TTC29ENST00000325106.9 linkuse as main transcriptc.1157A>C p.Glu386Ala missense_variant 11/131 NM_031956.4 ENSP00000316740 P4Q8NA56-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000124
AC:
3
AN:
241172
Hom.:
0
AF XY:
0.00000766
AC XY:
1
AN XY:
130606
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000169
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:
0.00000206
AC:
3
AN:
1455260
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
722990
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000758
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.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000828
AC:
1

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 submitterclinical testingAmbry GeneticsJun 22, 2023The c.1157A>C (p.E386A) alteration is located in exon 11 (coding exon 9) of the TTC29 gene. This alteration results from a A to C substitution at nucleotide position 1157, causing the glutamic acid (E) at amino acid position 386 to be replaced by an alanine (A). 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
0.098
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
8.4
DANN
Benign
0.63
DEOGEN2
Benign
0.0055
.;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.47
T;T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.2
.;L;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.12
Sift
Benign
0.20
T;T;T
Sift4G
Benign
0.51
T;T;T
Polyphen
0.0080
B;B;B
Vest4
0.13
MutPred
0.43
Loss of solvent accessibility (P = 0.0217);.;.;
MVP
0.30
MPC
0.015
ClinPred
0.017
T
GERP RS
0.79
Varity_R
0.039
gMVP
0.13

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.

Other links and lift over

dbSNP: rs773446493; hg19: chr4-147724782; API