5-177503990-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308236.3(DOK3):c.1316G>C(p.Arg439Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: DOK3 NM_001308236.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.724

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]

ACMG classification

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=0.17795005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK3	NM_001308236.3	c.1316G>C	p.Arg439Pro	missense_variant	6/6	ENST00000510898.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK3	ENST00000510898.7	c.1316G>C	p.Arg439Pro	missense_variant	6/6	3	NM_001308236.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152324 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74482

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.1484G>C (p.R495P) alteration is located in exon 6 (coding exon 6) of the DOK3 gene. This alteration results from a G to C substitution at nucleotide position 1484, causing the arginine (R) at amino acid position 495 to be replaced by a proline (P). 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	0.16
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T;T
Eigen	Benign	0.040
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.41	T
Polyphen		1.0	.;D;.
Vest4		0.24, 0.25
MutPred		0.27		.;Gain of relative solvent accessibility (P = 0.0098);.;
MVP		0.32
MPC		0.34
ClinPred		0.95	D
GERP RS		3.4
Varity_R		0.53
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-176930991;