Variant 14-103963088-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153046.3(TDRD9):c.332C>T(p.Pro111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000435 in 1,543,076 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

TDRD9
NM_153046.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.646

Variant links:

Genes affected

TDRD9 (HGNC:20122): (tudor domain containing 9) Predicted to enable RNA binding activity. Involved in spermatogenesis. Located in cytoplasm and nucleus. Implicated in spermatogenic failure 30. [provided by Alliance of Genome Resources, Apr 2022]

TDRD9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033640862).

BP6

Variant 14-103963088-C-T is Benign according to our data. Variant chr14-103963088-C-T is described in ClinVar as [Benign]. Clinvar id is 718196.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD9	NM_153046.3 linkuse as main transcript	c.332C>T	p.Pro111Leu	missense_variant	3/36	ENST00000409874.9	NP_694591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD9	ENST00000409874.9 linkuse as main transcript	c.332C>T	p.Pro111Leu	missense_variant	3/36	5	NM_153046.3	ENSP00000387303	P1	Q8NDG6-1
TDRD9	ENST00000496087.5 linkuse as main transcript	n.344C>T		non_coding_transcript_exon_variant	4/5	4
TDRD9	ENST00000554571.1 linkuse as main transcript	n.207C>T		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

357

AN:

151834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00833

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000723

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:

0.000480

GnomAD3 exomes

AF:

0.000537

AC:

AN:

149038

Hom.:

AF XY:

0.000329

AC XY:

AN XY:

79040

show subpopulations

Gnomad AFR exome

AF:

0.00931

Gnomad AMR exome

AF:

0.000269

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000479

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.000226

AC:

315

AN:

1391124

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

116

AN XY:

686068

show subpopulations

Gnomad4 AFR exome

AF:

0.00910

Gnomad4 AMR exome

AF:

0.000207

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000258

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.30e-7

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.00235

AC:

357

AN:

151952

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

169

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.00830

Gnomad4 AMR

AF:

0.000722

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:

0.000475

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.00271

ESP6500AA

AF:

0.00939

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000851

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 23, 2018

- -

TDRD9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.038

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.46

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

REVEL

Benign

0.056

Sift

Benign

0.17

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.059

MVP

0.13

MPC

0.21

ClinPred

0.0056

GERP RS

2.4

Varity_R

0.041

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over