chr10-114204822-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001395205.1(TDRD1):c.1226C>T(p.Ser409Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,334 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: 6.9e-7 ( 0 hom. )
Consequence
TDRD1
NM_001395205.1 missense
NM_001395205.1 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 0.996
Genes affected
TDRD1 (HGNC:11712): (tudor domain containing 1) This gene encodes a protein containing a tudor domain that is thought to function in the suppression of transposable elements during spermatogenesis. The related protein in mouse forms a complex with piRNAs and Piwi proteins to promote methylation and silencing of target sequences. This gene was observed to be upregulated by ETS transcription factor ERG in prostate tumors. [provided by RefSeq, Sep 2018]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.35654435).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TDRD1 | NM_001395205.1 | c.1226C>T | p.Ser409Phe | missense_variant | 10/25 | ENST00000695399.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TDRD1 | ENST00000695399.1 | c.1226C>T | p.Ser409Phe | missense_variant | 10/25 | NM_001395205.1 | P4 | ||
TDRD1 | ENST00000251864.7 | c.1226C>T | p.Ser409Phe | missense_variant | 10/26 | 1 | A2 | ||
TDRD1 | ENST00000369282.5 | c.1226C>T | p.Ser409Phe | missense_variant | 10/25 | 5 | A2 | ||
TDRD1 | ENST00000369280.1 | c.1226C>T | p.Ser409Phe | missense_variant | 10/24 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1448334Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 719480
GnomAD4 exome
AF:
AC:
1
AN:
1448334
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
719480
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
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 | Aug 01, 2022 | The c.1226C>T (p.S409F) alteration is located in exon 10 (coding exon 9) of the TDRD1 gene. This alteration results from a C to T substitution at nucleotide position 1226, causing the serine (S) at amino acid position 409 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
0.93
.;P;.
Vest4
MutPred
Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP
MPC
0.41
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at