rs8021692

Positions:

• chr14-103962239-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
TDRD9	NM_153046.3	c.323-840C>G		intron_variant		ENST00000409874.9	NP_694591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD9	ENST00000409874.9	c.323-840C>G		intron_variant		5	NM_153046.3	ENSP00000387303.4
TDRD9	ENST00000496087.5	n.335-840C>G		intron_variant		4
TDRD9	ENST00000554571.1	n.198-840C>G		intron_variant		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

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.277

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

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: rs8021692; hg19: chr14-104428576;