9-15186993-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152574.3(TTC39B):c.1240C>T(p.Pro414Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,613,204 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000049 ( 1 hom. )
Consequence
TTC39B
NM_152574.3 missense
NM_152574.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 2.33
Genes affected
TTC39B (HGNC:23704): (tetratricopeptide repeat domain 39B) Predicted to be involved in several processes, including cholesterol homeostasis; negative regulation of cholesterol storage; and regulation of cholesterol efflux. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC39B | NM_152574.3 | c.1240C>T | p.Pro414Ser | missense_variant | 15/20 | ENST00000512701.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC39B | ENST00000512701.7 | c.1240C>T | p.Pro414Ser | missense_variant | 15/20 | 2 | NM_152574.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152060Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250686Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135480
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GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461144Hom.: 1 Cov.: 30 AF XY: 0.0000523 AC XY: 38AN XY: 726866
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152060Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74274
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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 submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.1438C>T (p.P480S) alteration is located in exon 15 (coding exon 15) of the TTC39B gene. This alteration results from a C to T substitution at nucleotide position 1438, causing the proline (P) at amino acid position 480 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 42
Find out detailed SpliceAI scores and Pangolin per-transcript scores at