rs2616637

Variant names:

• chr10-114208672-C-A
• rs2616637
• NM_001395205.1:c.1385-1909C>A

Variant summary

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

The NM_001395205.1(TDRD1):​c.1385-1909C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,048 control chromosomes in the GnomAD database, including 17,587 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 (17587 hom., cov: 32)
• Consequence: TDRD1 NM_001395205.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720
• Publications: 1 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=-0.95).
• 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.1385-1909C>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.1385-1909C>A		intron_variant	Intron 11 of 24		NM_001395205.1	ENSP00000511878.1
TDRD1	ENST00000251864.7	c.1385-1909C>A		intron_variant	Intron 11 of 25	1		ENSP00000251864.2
TDRD1	ENST00000369282.5	c.1385-1909C>A		intron_variant	Intron 11 of 24	5		ENSP00000358288.1
TDRD1	ENST00000369280.1	c.1385-1909C>A		intron_variant	Intron 11 of 23	5		ENSP00000358286.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70950 AN: 151930 Hom.: 17539 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.467 AC: 71062 AN: 152048 Hom.: 17587 Cov.: 32 AF XY: 0.459 AC XY: 34117 AN XY: 74288

African (AFR) AF: 0.636 AC: 26364 AN: 41464

American (AMR) AF: 0.458 AC: 7003 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1512 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1022 AN: 5178

South Asian (SAS) AF: 0.308 AC: 1485 AN: 4818

European-Finnish (FIN) AF: 0.386 AC: 4073 AN: 10548

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28199 AN: 67982

Other (OTH) AF: 0.423 AC: 893 AN: 2112

Alfa AF: 0.454 Hom.: 2394

Bravo AF: 0.484

Asia WGS AF: 0.310 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.39
DANN	Benign	0.22
PhyloP100		-0.72
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: rs2616637; hg19: chr10-115968431;