rs11622475

Positions:

• chr14-104042739-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153046.3(TDRD9):​c.3974+552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,954 control chromosomes in the GnomAD database, including 4,836 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4836 hom., cov: 31)
• Consequence: TDRD9 NM_153046.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD9	NM_153046.3	c.3974+552C>T		intron_variant		ENST00000409874.9	NP_694591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD9	ENST00000409874.9	c.3974+552C>T		intron_variant		5	NM_153046.3	ENSP00000387303	P1
TDRD9	ENST00000557332.5	c.2580+552C>T		intron_variant		2		ENSP00000451637

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34977 AN: 151836 Hom.: 4835 Cov.: 31

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 34969 AN: 151954 Hom.: 4836 Cov.: 31 AF XY: 0.234 AC XY: 17354 AN XY: 74258

Gnomad4 AFR AF: 0.0763

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.270

Alfa AF: 0.285 Hom.: 8927

Bravo AF: 0.221

Asia WGS AF: 0.354 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.098
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs11622475; hg19: chr14-104509076;