10-114212236-A-G

Variant names:

• chr10-114212236-A-G
• rs10510000
• NM_001395205.1:c.1831+200A>G

Variant summary

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

The NM_001395205.1(TDRD1):​c.1831+200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,142 control chromosomes in the GnomAD database, including 2,029 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 0.16 (2029 hom., cov: 32)
• Consequence: TDRD1 NM_001395205.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD1	NM_001395205.1	c.1831+200A>G		intron_variant	Intron 14 of 24	ENST00000695399.1	NP_001382134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD1	ENST00000695399.1	c.1831+200A>G		intron_variant	Intron 14 of 24		NM_001395205.1	ENSP00000511878.1
TDRD1	ENST00000251864.7	c.1831+200A>G		intron_variant	Intron 14 of 25	1		ENSP00000251864.2
TDRD1	ENST00000369282.5	c.1831+200A>G		intron_variant	Intron 14 of 24	5		ENSP00000358288.1
TDRD1	ENST00000369280.1	c.1831+200A>G		intron_variant	Intron 14 of 23	5		ENSP00000358286.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23897 AN: 152024 Hom.: 2026 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.157 AC: 23929 AN: 152142 Hom.: 2029 Cov.: 32 AF XY: 0.156 AC XY: 11576 AN XY: 74390

African (AFR) AF: 0.188 AC: 7810 AN: 41498

American (AMR) AF: 0.142 AC: 2170 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3468

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5182

South Asian (SAS) AF: 0.0913 AC: 440 AN: 4818

European-Finnish (FIN) AF: 0.132 AC: 1393 AN: 10584

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10566 AN: 68000

Other (OTH) AF: 0.167 AC: 352 AN: 2114

Alfa AF: 0.167 Hom.: 2707

Bravo AF: 0.160

Asia WGS AF: 0.0570 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.065
DANN	Benign	0.58
PhyloP100		-1.3
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: rs10510000; hg19: chr10-115971995;