chr14-103998463-C-T

Variant names:

• chr14-103998463-C-T
• rs11625697
• NM_153046.3:c.1379-161C>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.1379-161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,034 control chromosomes in the GnomAD database, including 5,041 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 0.24 (5041 hom., cov: 30)
• Consequence: TDRD9 NM_153046.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 10 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 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.1379-161C>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.1379-161C>T		intron	N/A	ENSP00000387303.4
	TDRD9	ENST00000557332.5	TSL:2	c.557-161C>T		intron	N/A	ENSP00000451637.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36946 AN: 151916 Hom.: 5040 Cov.: 30

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.243 AC: 36950 AN: 152034 Hom.: 5041 Cov.: 30 AF XY: 0.246 AC XY: 18287 AN XY: 74316

African (AFR) AF: 0.120 AC: 4986 AN: 41480

American (AMR) AF: 0.247 AC: 3772 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1417 AN: 5160

South Asian (SAS) AF: 0.436 AC: 2096 AN: 4810

European-Finnish (FIN) AF: 0.261 AC: 2764 AN: 10574

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19766 AN: 67962

Other (OTH) AF: 0.276 AC: 580 AN: 2104

Alfa AF: 0.276 Hom.: 1439

Bravo AF: 0.236

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.010
DANN	Benign	0.69
PhyloP100		-2.7
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: rs11625697; hg19: chr14-104464800; COSMIC: COSV59155575;