rs998334

Variant names:

• chr10-114207253-G-A
• rs998334
• NM_001395205.1:c.1384+923G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-114207253-G-A
• chr10-114207253-G-C
• chr10-114207253-G-T

Variant summary

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

The NM_001395205.1(TDRD1):​c.1384+923G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,054 control chromosomes in the GnomAD database, including 17,516 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 0.47 (17516 hom., cov: 32)
• Consequence: TDRD1 NM_001395205.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD1	NM_001395205.1	c.1384+923G>A		intron_variant	Intron 11 of 24	ENST00000695399.1	NP_001382134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD1	ENST00000695399.1	c.1384+923G>A		intron_variant	Intron 11 of 24		NM_001395205.1	ENSP00000511878.1
TDRD1	ENST00000251864.7	c.1384+923G>A		intron_variant	Intron 11 of 25	1		ENSP00000251864.2
TDRD1	ENST00000369282.5	c.1384+923G>A		intron_variant	Intron 11 of 24	5		ENSP00000358288.1
TDRD1	ENST00000369280.1	c.1384+923G>A		intron_variant	Intron 11 of 23	5		ENSP00000358286.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70772 AN: 151936 Hom.: 17468 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.466 AC: 70885 AN: 152054 Hom.: 17516 Cov.: 32 AF XY: 0.458 AC XY: 34049 AN XY: 74324

African (AFR) AF: 0.635 AC: 26355 AN: 41494

American (AMR) AF: 0.458 AC: 6989 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1511 AN: 3470

East Asian (EAS) AF: 0.180 AC: 930 AN: 5168

South Asian (SAS) AF: 0.308 AC: 1488 AN: 4824

European-Finnish (FIN) AF: 0.386 AC: 4070 AN: 10556

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28137 AN: 67956

Other (OTH) AF: 0.422 AC: 893 AN: 2114

Alfa AF: 0.452 Hom.: 2549

Bravo AF: 0.482

Asia WGS AF: 0.303 AC: 1053 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.41
PhyloP100		-0.26
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: rs998334; hg19: chr10-115967012;