14-103965536-A-T

Position:

• chr14-103965536-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_153046.3(TDRD9):​c.624A>T​(p.Gly208Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TDRD9 NM_153046.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.58

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 14-103965536-A-T is Benign according to our data. Variant chr14-103965536-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041885.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.58 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD9	NM_153046.3	c.624A>T	p.Gly208Gly	synonymous_variant	4/36	ENST00000409874.9	NP_694591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD9	ENST00000409874.9	c.624A>T	p.Gly208Gly	synonymous_variant	4/36	5	NM_153046.3	ENSP00000387303.4
TDRD9	ENST00000554571.1	n.499A>T		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 59 AN: 142068 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000377

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000351

Gnomad ASJ AF: 0.000302

Gnomad EAS AF: 0.00196

Gnomad SAS AF: 0.000260

Gnomad FIN AF: 0.000113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000432

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00379 AC: 4103 AN: 1083626 Hom.: 0 Cov.: 33 AF XY: 0.00412 AC XY: 2205 AN XY: 535386

Gnomad4 AFR exome AF: 0.00577

Gnomad4 AMR exome AF: 0.00442

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.0159

Gnomad4 SAS exome AF: 0.000507

Gnomad4 FIN exome AF: 0.00418

Gnomad4 NFE exome AF: 0.00347

Gnomad4 OTH exome AF: 0.00756

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000422 AC: 60 AN: 142214 Hom.: 0 Cov.: 32 AF XY: 0.000506 AC XY: 35 AN XY: 69148

Gnomad4 AFR AF: 0.000401

Gnomad4 AMR AF: 0.000350

Gnomad4 ASJ AF: 0.000302

Gnomad4 EAS AF: 0.00195

Gnomad4 SAS AF: 0.000259

Gnomad4 FIN AF: 0.000113

Gnomad4 NFE AF: 0.000432

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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	0.89
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

Other links and lift over

dbSNP: rs2032701619; hg19: chr14-104431873;