10-114187922-A-T

Variant summary

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

The NM_001395205.1(TDRD1):​c.91A>T​(p.Asn31Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TDRD1
NM_001395205.1 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.677
Variant links:
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]

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=0.16126227).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TDRD1NM_001395205.1 linkuse as main transcriptc.91A>T p.Asn31Tyr missense_variant 2/25 ENST00000695399.1 NP_001382134.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TDRD1ENST00000695399.1 linkuse as main transcriptc.91A>T p.Asn31Tyr missense_variant 2/25 NM_001395205.1 ENSP00000511878.1 Q9BXT4-1
TDRD1ENST00000251864.7 linkuse as main transcriptc.91A>T p.Asn31Tyr missense_variant 2/261 ENSP00000251864.2 Q9BXT4-3
TDRD1ENST00000369282.5 linkuse as main transcriptc.91A>T p.Asn31Tyr missense_variant 2/255 ENSP00000358288.1 H9KV63
TDRD1ENST00000369280.1 linkuse as main transcriptc.91A>T p.Asn31Tyr missense_variant 2/245 ENSP00000358286.1 H9KV62

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250310
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135330
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1460938
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726822
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 GeneticsOct 16, 2024The c.91A>T (p.N31Y) alteration is located in exon 2 (coding exon 1) of the TDRD1 gene. This alteration results from a A to T substitution at nucleotide position 91, causing the asparagine (N) at amino acid position 31 to be replaced by a tyrosine (Y). 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
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
22
DANN
Uncertain
0.99
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.69
T;T;T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
.;M;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.011
D;D;D
Sift4G
Uncertain
0.019
D;D;D
Polyphen
0.99
.;D;.
Vest4
0.34
MutPred
0.069
Gain of phosphorylation at N31 (P = 0.0857);Gain of phosphorylation at N31 (P = 0.0857);Gain of phosphorylation at N31 (P = 0.0857);
MVP
0.26
MPC
0.81
ClinPred
0.79
D
GERP RS
4.4
gMVP
0.27

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

LitVar

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

Other links and lift over

dbSNP: rs910414280; hg19: chr10-115947681; API