Genetic Variant TDRD1:c.-126T>C (chr10-114179297-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000251864.7(TDRD1):c.-126T>C variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

3 publications found

Variant links:

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]

TDRD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TDRD1	NM_001395205.1 link	c.-126T>C		upstream_gene_variant		ENST00000695399.1	NP_001382134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD1	ENST00000695399.1 link	c.-126T>C		upstream_gene_variant			NM_001395205.1	ENSP00000511878.1		Q9BXT4-1

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1947

AN:

152170

Hom.:

179

Cov.:

show subpopulations

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:

AN:

374

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

AN XY:

292

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

304

Other (OTH)

AF:

0.0385

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.022510), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0128

AC:

1945

AN:

152288

Hom.:

179

Cov.:

AF XY:

0.0143

AC XY:

1063

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41584

American (AMR)

AF:

0.0233

AC:

357

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.254

AC:

1313

AN:

5162

South Asian (SAS)

AF:

0.00994

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00783

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

68016

Other (OTH)

AF:

0.0118

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

167

250

334

417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00134

Hom.:

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

(source)

DANN

Benign

0.37

PhyloP100

-1.4

PromoterAI

0.041

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over