1-179593582-C-T

Variant summary

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

The NM_001199085.3(TDRD5):​c.355C>T​(p.Arg119Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TDRD5
NM_001199085.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
Variant links:
Genes affected
TDRD5 (HGNC:20614): (tudor domain containing 5) Predicted to be involved in DNA methylation involved in gamete generation; P granule organization; and spermatid development. Predicted to be located in chromatoid body and pi-body. [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=0.12511408).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TDRD5NM_001199085.3 linkc.355C>T p.Arg119Trp missense_variant Exon 3 of 18 ENST00000444136.6 NP_001186014.1 Q8NAT2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TDRD5ENST00000444136.6 linkc.355C>T p.Arg119Trp missense_variant Exon 3 of 18 1 NM_001199085.3 ENSP00000406052.1 Q8NAT2-1
TDRD5ENST00000294848.12 linkc.355C>T p.Arg119Trp missense_variant Exon 3 of 17 1 ENSP00000294848.8 Q8NAT2-3
TDRD5ENST00000367614.5 linkc.355C>T p.Arg119Trp missense_variant Exon 3 of 17 2 ENSP00000356586.1 Q8NAT2-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251482
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461886
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.355C>T (p.R119W) alteration is located in exon 3 (coding exon 2) of the TDRD5 gene. This alteration results from a C to T substitution at nucleotide position 355, causing the arginine (R) at amino acid position 119 to be replaced by a tryptophan (W). 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
0.11
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;.;T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.82
.;T;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;L;L
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-2.2
N;N;N
REVEL
Benign
0.089
Sift
Benign
0.035
D;D;D
Sift4G
Uncertain
0.034
D;D;D
Polyphen
0.93
P;D;P
Vest4
0.18
MutPred
0.40
Loss of disorder (P = 0.0023);Loss of disorder (P = 0.0023);Loss of disorder (P = 0.0023);
MVP
0.043
MPC
0.55
ClinPred
0.25
T
GERP RS
3.8
Varity_R
0.11
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748631957; hg19: chr1-179562717; COSMIC: COSV99675077; COSMIC: COSV99675077; API