Genetic Variant TDRKH:c.1045-85C>T (chr1-151776353-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001083965.2(TDRKH):c.1045-85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,593,974 control chromosomes in the GnomAD database, including 7,246 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 0.039 ( 722 hom., cov: 32)

Exomes 𝑓: 0.035 ( 6524 hom. )

Consequence

TDRKH
NM_001083965.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.407

Publications

5 publications found

Variant links:

Genes affected

TDRKH (HGNC:11713): (tudor and KH domain containing) Predicted to enable RNA binding activity. Predicted to be involved in fertilization; gamete generation; and piRNA metabolic process. Predicted to be located in mitochondrion; pi-body; and piP-body. [provided by Alliance of Genome Resources, Apr 2022]

TDRKH 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083965.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TDRKH	NM_001083965.2	MANE Select	c.1045-85C>T	intron	N/A	NP_001077434.1
TDRKH	NM_001083963.1		c.1045-85C>T	intron	N/A	NP_001077432.1
TDRKH	NM_006862.4		c.1045-85C>T	intron	N/A	NP_006853.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TDRKH	ENST00000368824.8	TSL:1 MANE Select	c.1045-85C>T	intron	N/A	ENSP00000357815.3
TDRKH	ENST00000368827.10	TSL:1	c.1045-85C>T	intron	N/A	ENSP00000357819.6
TDRKH	ENST00000458431.6	TSL:1	c.1045-85C>T	intron	N/A	ENSP00000395718.2

Frequencies

GnomAD3 genomes

AF:

0.0392

AC:

5969

AN:

152140

Hom.:

726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00465

Gnomad OTH

AF:

0.0482

GnomAD4 exome

AF:

0.0347

AC:

49973

AN:

1441716

Hom.:

6524

Cov.:

AF XY:

0.0389

AC XY:

27836

AN XY:

714988

show subpopulations

African (AFR)

AF:

0.0171

AC:

559

AN:

32722

American (AMR)

AF:

0.227

AC:

9652

AN:

42522

Ashkenazi Jewish (ASJ)

AF:

0.00264

AC:

AN:

24966

East Asian (EAS)

AF:

0.361

AC:

14206

AN:

39406

South Asian (SAS)

AF:

0.221

AC:

18507

AN:

83712

European-Finnish (FIN)

AF:

0.000492

AC:

AN:

52794

Middle Eastern (MID)

AF:

0.0282

AC:

159

AN:

5648

European-Non Finnish (NFE)

AF:

0.00365

AC:

4018

AN:

1100558

Other (OTH)

AF:

0.0468

AC:

2780

AN:

59388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2242

4484

6727

8969

11211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

694

1388

2082

2776

3470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0391

AC:

5955

AN:

152258

Hom.:

722

Cov.:

AF XY:

0.0457

AC XY:

3401

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0165

AC:

686

AN:

41562

American (AMR)

AF:

0.111

AC:

1692

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.392

AC:

2028

AN:

5180

South Asian (SAS)

AF:

0.230

AC:

1107

AN:

4810

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00465

AC:

316

AN:

68018

Other (OTH)

AF:

0.0482

AC:

102

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

237

474

710

947

1184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0227

Hom.:

348

Bravo

AF:

0.0499

Asia WGS

AF:

0.247

AC:

858

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

(source)

DANN

Benign

0.39

PhyloP100

-0.41

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over