Genetic Variant ENST00000251864.7: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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new If you want to explore the variant's impact on the transcript ENST00000251864.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000251864.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
TDRD1	NM_001385363.1	c.-93T>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	NP_001372292.1	Q9BXT4-3
TDRD1	NM_198795.2	c.-126T>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	NP_942090.1	Q9BXT4-3
TDRD1	NM_001385365.1	c.-126T>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 25	NP_001372294.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TDRD1	ENST00000251864.7	TSL:1	c.-126T>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000251864.2	Q9BXT4-3
TDRD1	ENST00000251864.7	TSL:1	c.-126T>C	5_prime_UTR	Exon 1 of 26	ENSP00000251864.2	Q9BXT4-3
TDRD1	ENST00000860255.1		c.-126T>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 24	ENSP00000530314.1

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 = 0.0225104), 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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over