Variant 5-177503139-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000312943.10(DOK3):c.899A>G(p.Gln300Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,549,548 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 2 hom. )

Consequence

DOK3
ENST00000312943.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.161

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006062627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK3	NM_001308236.3 linkuse as main transcript	c.*844A>G		3_prime_UTR_variant	6/6	ENST00000510898.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK3	ENST00000510898.7 linkuse as main transcript	c.*844A>G		3_prime_UTR_variant	6/6	3	NM_001308236.3	P1
PDLIM7-AS1	ENST00000506025.1 linkuse as main transcript	n.145-219T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

191

AN:

150092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000332

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00335

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.00146

GnomAD3 exomes

AF:

0.00109

AC:

165

AN:

151368

Hom.:

AF XY:

0.00102

AC XY:

AN XY:

80524

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000568

Gnomad ASJ exome

AF:

0.000945

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000879

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00148

AC:

2071

AN:

1399338

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1037

AN XY:

690186

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000560

Gnomad4 ASJ exome

AF:

0.000755

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.00225

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.000914

GnomAD4 genome

AF:

0.00127

AC:

191

AN:

150210

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

AN XY:

73282

show subpopulations

Gnomad4 AFR

AF:

0.000270

Gnomad4 AMR

AF:

0.000331

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00335

Gnomad4 NFE

AF:

0.00203

Gnomad4 OTH

AF:

0.00145

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00107

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00259

AC:

ExAC

AF:

0.000898

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.899A>G (p.Q300R) alteration is located in exon 6 (coding exon 5) of the DOK3 gene. This alteration results from a A to G substitution at nucleotide position 899, causing the glutamine (Q) at amino acid position 300 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

Cadd

Benign

0.74

Dann

Benign

0.94

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0061

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.54

N;N

REVEL

Benign

0.013

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.029

D;D

Polyphen

0.044

B;.

Vest4

0.10

MVP

0.15

ClinPred

0.0029

GERP RS

-0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over