Genetic Variant NM_001308236.3:c.*215G>A (chr5-177503768-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001308236.3(DOK3):c.*215G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,418,996 control chromosomes in the GnomAD database, including 2,137 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 0.031 ( 333 hom., cov: 33)

Exomes 𝑓: 0.015 ( 1804 hom. )

Consequence

DOK3
NM_001308236.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

4 publications found

Variant links:

Genes affected

DOK3 (HGNC:24583): (docking protein 3) Predicted to be involved in Ras protein signal transduction and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be located in ficolin-1-rich granule membrane and plasma membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DOK3 links:

PDLIM7-AS1 (HGNC:41004): (PDLIM7 antisense RNA 1)

PDLIM7-AS1 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK3	NM_001308236.3 link	c.*215G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000510898.7	NP_001295165.1	Q7L591D6RAM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK3	ENST00000510898.7 link	c.*215G>A		3_prime_UTR_variant	Exon 6 of 6	3	NM_001308236.3	ENSP00000424726.2		D6RAM3

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4693

AN:

152154

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0293

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0728

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.0694

Gnomad FIN

AF:

0.0285

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.0368

GnomAD4 exome

AF:

0.0154

AC:

19524

AN:

1266724

Hom.:

1804

Cov.:

AF XY:

0.0162

AC XY:

9936

AN XY:

612132

show subpopulations

African (AFR)

AF:

0.0295

AC:

824

AN:

27908

American (AMR)

AF:

0.0988

AC:

1699

AN:

17194

Ashkenazi Jewish (ASJ)

AF:

0.00150

AC:

AN:

18676

East Asian (EAS)

AF:

0.297

AC:

9984

AN:

33624

South Asian (SAS)

AF:

0.0567

AC:

3383

AN:

59654

European-Finnish (FIN)

AF:

0.0251

AC:

740

AN:

29454

Middle Eastern (MID)

AF:

0.00932

AC:

AN:

3540

European-Non Finnish (NFE)

AF:

0.00129

AC:

1321

AN:

1024144

Other (OTH)

AF:

0.0288

AC:

1512

AN:

52530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

858

1716

2573

3431

4289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.0308

AC:

4696

AN:

152272

Hom.:

333

Cov.:

AF XY:

0.0342

AC XY:

2548

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0293

AC:

1218

AN:

41564

American (AMR)

AF:

0.0727

AC:

1112

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.287

AC:

1479

AN:

5162

South Asian (SAS)

AF:

0.0697

AC:

336

AN:

4822

European-Finnish (FIN)

AF:

0.0285

AC:

302

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00240

AC:

163

AN:

68016

Other (OTH)

AF:

0.0369

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

215

430

646

861

1076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0141

Hom.:

122

Bravo

AF:

0.0372

Asia WGS

AF:

0.149

AC:

516

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.13

(source)

DANN

Benign

0.60

PhyloP100

-1.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over