18-24080743-G-T

Variant summary

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

The NM_001135993.2(TTC39C):​c.619G>T​(p.Val207Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,876 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TTC39C
NM_001135993.2 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38
Variant links:
Genes affected
TTC39C (HGNC:26595): (tetratricopeptide repeat domain 39C) Predicted to be involved in cilium assembly and otolith morphogenesis. [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=0.23037341).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TTC39CNM_001135993.2 linkuse as main transcriptc.619G>T p.Val207Leu missense_variant 5/14 ENST00000317571.8 NP_001129465.1 Q8N584-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TTC39CENST00000317571.8 linkuse as main transcriptc.619G>T p.Val207Leu missense_variant 5/141 NM_001135993.2 ENSP00000323645.3 Q8N584-1
TTC39CENST00000304621.10 linkuse as main transcriptc.436G>T p.Val146Leu missense_variant 5/141 ENSP00000306598.6 Q8N584-2
TTC39CENST00000578150.1 linkuse as main transcriptn.463G>T non_coding_transcript_exon_variant 4/43
ENSG00000265204ENST00000578443.1 linkuse as main transcriptn.99-3484C>A intron_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461876
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

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 GeneticsFeb 07, 2023The c.619G>T (p.V207L) alteration is located in exon 5 (coding exon 5) of the TTC39C gene. This alteration results from a G to T substitution at nucleotide position 619, causing the valine (V) at amino acid position 207 to be replaced by a leucine (L). 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
0.13
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.026
.;T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.85
D;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.73
N;N
REVEL
Benign
0.15
Sift
Uncertain
0.023
D;D
Sift4G
Uncertain
0.036
D;D
Polyphen
0.50
.;P
Vest4
0.12
MutPred
0.52
.;Gain of helix (P = 0.0696);
MVP
0.70
MPC
0.48
ClinPred
0.65
D
GERP RS
5.9
Varity_R
0.28
gMVP
0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-21660707; API