rs17091424

Positions:

• chr10-114206388-C-G
• chr10-114206388-C-T

Variant summary

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

The NM_001395205.1(TDRD1):​c.1384+58C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,407,726 control chromosomes in the GnomAD database, including 36,376 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 0.22 (3837 hom., cov: 32)
  • Exomes 𝑓: 0.22 (32539 hom.)
• Consequence: TDRD1 NM_001395205.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

Genes affected

TDRD1 (HGNC:11712): (tudor domain containing 1) This gene encodes a protein containing a tudor domain that is thought to function in the suppression of transposable elements during spermatogenesis. The related protein in mouse forms a complex with piRNAs and Piwi proteins to promote methylation and silencing of target sequences. This gene was observed to be upregulated by ETS transcription factor ERG in prostate tumors. [provided by RefSeq, Sep 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD1	NM_001395205.1	c.1384+58C>G		intron_variant		ENST00000695399.1	NP_001382134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD1	ENST00000695399.1	c.1384+58C>G		intron_variant			NM_001395205.1	ENSP00000511878	P4
TDRD1	ENST00000251864.7	c.1384+58C>G		intron_variant		1		ENSP00000251864	A2
TDRD1	ENST00000369280.1	c.1384+58C>G		intron_variant		5		ENSP00000358286	A2
TDRD1	ENST00000369282.5	c.1384+58C>G		intron_variant		5		ENSP00000358288	A2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33520 AN: 151934 Hom.: 3833 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.0714

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.223 AC: 279586 AN: 1255672 Hom.: 32539 AF XY: 0.220 AC XY: 139558 AN XY: 633188

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.0771

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.221 AC: 33566 AN: 152054 Hom.: 3837 Cov.: 32 AF XY: 0.219 AC XY: 16257 AN XY: 74306

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.0718

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.222

Alfa AF: 0.123 Hom.: 195

Bravo AF: 0.222

Asia WGS AF: 0.125 AC: 437 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.33

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: rs17091424; hg19: chr10-115966147; COSMIC: COSV52591533;