Variant 14-103965330-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_153046.3(TDRD9):c.421-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,551,490 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

TDRD9
NM_153046.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009610

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.56

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 14-103965330-T-C is Benign according to our data. Variant chr14-103965330-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3035459.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD9	NM_153046.3 linkuse as main transcript	c.421-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000409874.9	NP_694591.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
TDRD9	ENST00000409874.9 linkuse as main transcript	c.421-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_153046.3	ENSP00000387303	P1	Q8NDG6-1
TDRD9	ENST00000496087.5 linkuse as main transcript	n.433-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	4
TDRD9	ENST00000554571.1 linkuse as main transcript	n.296-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000518

AC:

AN:

156482

Hom.:

AF XY:

0.000518

AC XY:

AN XY:

82954

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.000568

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000909

Gnomad OTH exome

AF:

0.00136

GnomAD4 exome

AF:

0.00117

AC:

1641

AN:

1399142

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

806

AN XY:

690036

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.000588

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

AF:

0.000624

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000916

Hom.:

Bravo

AF:

0.000703

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TDRD9-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.6

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000096

dbscSNV1_RF

Benign

0.034

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.

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