rs11622475

Variant names:

• chr14-104042739-C-T
• rs11622475
• NM_153046.3:c.3974+552C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 30

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153046.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD9	NM_153046.3	MANE Select	c.3974+552C>T		intron	N/A	NP_694591.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD9	ENST00000409874.9	TSL:5 MANE Select	c.3974+552C>T		intron	N/A	ENSP00000387303.4
	TDRD9	ENST00000557332.5	TSL:2	c.2579+552C>T		intron	N/A	ENSP00000451637.1

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

African (AFR) AF: 0.0763 AC: 3168 AN: 41494

American (AMR) AF: 0.243 AC: 3716 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1205 AN: 3464

East Asian (EAS) AF: 0.273 AC: 1398 AN: 5128

South Asian (SAS) AF: 0.434 AC: 2088 AN: 4806

European-Finnish (FIN) AF: 0.260 AC: 2743 AN: 10560

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.290 AC: 19725 AN: 67906

Other (OTH) AF: 0.270 AC: 567 AN: 2102

Alfa AF: 0.270 Hom.: 13213

Bravo AF: 0.221

Asia WGS AF: 0.354 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.098
DANN	Benign	0.30
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11622475; hg19: chr14-104509076;