chr14-103962239-C-G

Variant names:

• chr14-103962239-C-G
• rs8021692
• NM_153046.3:c.323-840C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153046.3(TDRD9):​c.323-840C>G 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 152,066 control chromosomes in the GnomAD database, including 5,050 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 (5050 hom., cov: 32)
• Consequence: TDRD9 NM_153046.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• Publications: 13 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD9	NM_153046.3	c.323-840C>G		intron_variant	Intron 2 of 35	ENST00000409874.9	NP_694591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD9	ENST00000409874.9	c.323-840C>G		intron_variant	Intron 2 of 35	5	NM_153046.3	ENSP00000387303.4
TDRD9	ENST00000496087.5	n.335-840C>G		intron_variant	Intron 3 of 4	4
TDRD9	ENST00000554571.1	n.198-840C>G		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36985 AN: 151948 Hom.: 5049 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.243 AC: 36989 AN: 152066 Hom.: 5050 Cov.: 32 AF XY: 0.246 AC XY: 18314 AN XY: 74322

African (AFR) AF: 0.120 AC: 4971 AN: 41504

American (AMR) AF: 0.248 AC: 3782 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1458 AN: 5160

South Asian (SAS) AF: 0.436 AC: 2100 AN: 4818

European-Finnish (FIN) AF: 0.260 AC: 2748 AN: 10558

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

European-Non Finnish (NFE) AF: 0.291 AC: 19785 AN: 67982

Other (OTH) AF: 0.277 AC: 583 AN: 2108

Alfa AF: 0.270 Hom.: 756

Bravo AF: 0.236

Asia WGS AF: 0.363 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.37
DANN	Benign	0.36
PhyloP100		-0.89
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: rs8021692; hg19: chr14-104428576;