Variant 5-177504026-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001308236.3(DOK3):c.1280G>A(p.Ser427Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,582,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

DOK3
NM_001308236.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

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:

DOK3 (HGNC:):

DOK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15650275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK3	NM_001308236.3 linkuse as main transcript	c.1280G>A	p.Ser427Asn	missense_variant	6/6	ENST00000510898.7	NP_001295165.1	Q7L591D6RAM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK3	ENST00000510898.7 linkuse as main transcript	c.1280G>A	p.Ser427Asn	missense_variant	6/6	3	NM_001308236.3	ENSP00000424726.2		D6RAM3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000252

AC:

AN:

198550

Hom.:

AF XY:

0.0000465

AC XY:

AN XY:

107450

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000588

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000706

AC:

101

AN:

1430012

Hom.:

Cov.:

AF XY:

0.0000607

AC XY:

AN XY:

708910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000867

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000166

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

Nov 20, 2023

The c.1448G>A (p.S483N) alteration is located in exon 6 (coding exon 6) of the DOK3 gene. This alteration results from a G to A substitution at nucleotide position 1448, causing the serine (S) at amino acid position 483 to be replaced by an asparagine (N). 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

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.042

T;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.69

.;T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;M;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.085

Sift

Uncertain

0.0080

.;D;D

Sift4G

Uncertain

0.017

.;D;D

Polyphen

0.61

.;P;.

Vest4

0.17, 0.19

MVP

0.30

MPC

0.15

ClinPred

0.22

GERP RS

3.7

Varity_R

0.13

gMVP

0.51

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

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