chr13-60528822-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001146070.2(TDRD3):c.1597C>T(p.Arg533Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000093 in 1,613,424 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
TDRD3
NM_001146070.2 missense
NM_001146070.2 missense
Scores
7
8
4
Clinical Significance
Conservation
PhyloP100: 3.41
Genes affected
TDRD3 (HGNC:20612): (tudor domain containing 3) Enables chromatin binding activity; methylated histone binding activity; and transcription coactivator activity. Predicted to be involved in chromatin organization and positive regulation of transcription, DNA-templated. Located in Golgi apparatus; cytosol; and nucleoplasm. Colocalizes with exon-exon junction complex. [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 |
---|---|---|---|---|---|---|---|
TDRD3 | NM_001146070.2 | c.1597C>T | p.Arg533Cys | missense_variant | 11/14 | ENST00000377881.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TDRD3 | ENST00000377881.8 | c.1597C>T | p.Arg533Cys | missense_variant | 11/14 | 1 | NM_001146070.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151984Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249612Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135272
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GnomAD4 exome AF: 0.0000985 AC: 144AN: 1461440Hom.: 0 Cov.: 32 AF XY: 0.0000757 AC XY: 55AN XY: 726966
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151984Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74240
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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 | Dec 07, 2021 | The c.1597C>T (p.R533C) alteration is located in exon 11 (coding exon 11) of the TDRD3 gene. This alteration results from a C to T substitution at nucleotide position 1597, causing the arginine (R) at amino acid position 533 to be replaced by a cysteine (C). 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
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.;T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;.;.;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.;M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;.;.
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;.;.
Sift4G
Pathogenic
D;D;D;D;.;D
Polyphen
D;D;D;D;D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.036);Loss of MoRF binding (P = 0.036);.;Loss of MoRF binding (P = 0.036);Loss of MoRF binding (P = 0.036);.;
MVP
MPC
0.76
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at