10-114179297-T-C

Variant summary

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

The ENST00000251864.7(TDRD1):c.-126T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 152,662 control chromosomes in the GnomAD database, including 179 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 0.013 (179 hom., cov: 33)
  • Exomes 𝑓: 0.0080 (0 hom.)
• Consequence: TDRD1 ENST00000251864.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD1	NM_001385363.1	c.-93T>C		5_prime_UTR_variant	1/26
TDRD1	NM_001385365.1	c.-126T>C		5_prime_UTR_variant	1/25
TDRD1	NM_001385366.1	c.-126T>C		5_prime_UTR_variant	1/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD1	ENST00000251864.7	c.-126T>C		5_prime_UTR_variant	1/26	1		A2
TDRD1	ENST00000369282.5	c.-126T>C		5_prime_UTR_variant	1/25	5		A2

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1947 AN: 152170 Hom.: 179 Cov.: 33

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00783

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00802 AC: 3 AN: 374 Hom.: 0 Cov.: 0 AF XY: 0.0103 AC XY: 3 AN XY: 292

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0385

GnomAD4 genome AF: 0.0128 AC: 1945 AN: 152288 Hom.: 179 Cov.: 33 AF XY: 0.0143 AC XY: 1063 AN XY: 74462

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.00994

Gnomad4 FIN AF: 0.00783

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00134 Hom.: 1

Bravo AF: 0.0150

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.096
Dann	Benign	0.37

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: rs77559927; hg19: chr10-115939056;