Genetic Variant TDRD9:p.Ser177Ser (chr14-103965443-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_153046.3(TDRD9):c.531C>T(p.Ser177Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,551,538 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

TDRD9
NM_153046.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.87

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 14-103965443-C-T is Benign according to our data. Variant chr14-103965443-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049271.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.87 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD9	NM_153046.3 link	c.531C>T	p.Ser177Ser	synonymous_variant	Exon 4 of 36	ENST00000409874.9	NP_694591.2	Q8NDG6-1Q86WA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TDRD9	ENST00000409874.9 link	c.531C>T	p.Ser177Ser	synonymous_variant	Exon 4 of 36	5	NM_153046.3	ENSP00000387303.4	Q8NDG6-1
TDRD9	ENST00000496087.5 link	n.543C>T		non_coding_transcript_exon_variant	Exon 5 of 5	4
TDRD9	ENST00000554571.1 link	n.406C>T		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000428

AC:

AN:

156584

Hom.:

AF XY:

0.000482

AC XY:

AN XY:

82988

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00612

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000198

Gnomad OTH exome

AF:

0.000455

GnomAD4 exome

AF:

0.000192

AC:

268

AN:

1399406

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

150

AN XY:

690210

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00691

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000491

Gnomad4 OTH exome

AF:

0.000586

GnomAD4 genome

AF:

0.000270

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000461

Hom.:

Bravo

AF:

0.000268

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TDRD9-related disorder

Benign:1

Dec 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.73

CADD

Benign

0.37

DANN

Benign

0.69

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.

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