1-154547421-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182499.4(TDRD10):​c.965C>T​(p.Ser322Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,614,034 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TDRD10
NM_182499.4 missense

Scores

1
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.455
Variant links:
Genes affected
TDRD10 (HGNC:25316): (tudor domain containing 10) Predicted to enable RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06503856).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TDRD10NM_182499.4 linkuse as main transcriptc.965C>T p.Ser322Leu missense_variant 12/13 ENST00000368482.8 NP_872305.3 Q5VZ19-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TDRD10ENST00000368482.8 linkuse as main transcriptc.965C>T p.Ser322Leu missense_variant 12/131 NM_182499.4 ENSP00000357467.4 Q5VZ19-2
TDRD10ENST00000479937.5 linkuse as main transcriptn.710C>T non_coding_transcript_exon_variant 7/81
TDRD10ENST00000368480.3 linkuse as main transcriptc.965C>T p.Ser322Leu missense_variant 12/122 ENSP00000357465.3 Q5VZ19-1
TDRD10ENST00000468714.5 linkuse as main transcriptn.514C>T non_coding_transcript_exon_variant 6/65

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152154
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250978
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135716
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:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74330
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3

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 GeneticsApr 24, 2024The c.965C>T (p.S322L) alteration is located in exon 12 (coding exon 11) of the TDRD10 gene. This alteration results from a C to T substitution at nucleotide position 965, causing the serine (S) at amino acid position 322 to be replaced by a leucine (L). 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
0.17
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0024
.;T
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.065
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.0
L;L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.99
N;N
REVEL
Benign
0.069
Sift
Pathogenic
0.0
D;D
Polyphen
0.098
B;B
Vest4
0.55
MVP
0.085
MPC
0.91
ClinPred
0.28
T
GERP RS
3.2
Varity_R
0.11
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs372155332; hg19: chr1-154519897; COSMIC: COSV52724747; COSMIC: COSV52724747; API