chr1-2641718-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001242672.3(TTC34):​c.2890C>A​(p.Leu964Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000795 in 1,383,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

TTC34
NM_001242672.3 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.482

Publications

0 publications found
Variant links:
Genes affected
TTC34 (HGNC:34297): (tetratricopeptide repeat domain 34)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13687485).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTC34NM_001242672.3 linkc.2890C>A p.Leu964Ile missense_variant Exon 9 of 9 ENST00000401095.9 NP_001229601.2 A8MYJ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTC34ENST00000401095.9 linkc.2890C>A p.Leu964Ile missense_variant Exon 9 of 9 5 NM_001242672.3 ENSP00000383873.4 A0A1C7CYW7
TTC34ENST00000637179.1 linkc.1351C>A p.Leu451Ile missense_variant Exon 7 of 7 5 ENSP00000490537.1 A8MYJ7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000795
AC:
11
AN:
1383234
Hom.:
0
Cov.:
30
AF XY:
0.00000733
AC XY:
5
AN XY:
682538
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31586
American (AMR)
AF:
0.00
AC:
0
AN:
35680
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25156
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35722
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79226
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33640
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5660
European-Non Finnish (NFE)
AF:
0.0000102
AC:
11
AN:
1078692
Other (OTH)
AF:
0.00
AC:
0
AN:
57872
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 11, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1351C>A (p.L451I) alteration is located in exon 7 (coding exon 7) of the TTC34 gene. This alteration results from a C to A substitution at nucleotide position 1351, causing the leucine (L) at amino acid position 451 to be replaced by an isoleucine (I). 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
0.10
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
9.8
DANN
Benign
0.78
DEOGEN2
Benign
0.0062
.;T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.56
T;.
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
.;L
PhyloP100
0.48
PrimateAI
Uncertain
0.65
T
REVEL
Benign
0.10
MutPred
0.52
.;Loss of disorder (P = 0.0474);
MVP
0.14
ClinPred
0.076
T
GERP RS
2.8
Varity_R
0.064
gMVP
0.10
Mutation Taster
=97/3
polymorphism

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

Other links and lift over

dbSNP: rs1020030936; hg19: chr1-2573157; API