Genetic Variant DCLK3:p.Glu491Gln (chr3-36737696-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394672.2(DCLK3):c.1471G>C(p.Glu491Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E491K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DCLK3
NM_001394672.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

Publications

0 publications found

Variant links:

Genes affected

DCLK3 (HGNC:19005): (doublecortin like kinase 3) Predicted to enable protein kinase activity. Predicted to be involved in peptidyl-serine phosphorylation. Predicted to act upstream of or within negative regulation of protein localization to nucleus. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DCLK3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21564937).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394672.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK3	NM_001394672.2	MANE Select	c.1471G>C	p.Glu491Gln	missense	Exon 2 of 5	NP_001381601.1	A0A1B0GTZ4
	DCLK3	NM_033403.1		c.964G>C	p.Glu322Gln	missense	Exon 2 of 5	NP_208382.1	Q9C098

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCLK3	ENST00000636136.2	TSL:5 MANE Select	c.1471G>C	p.Glu491Gln	missense	Exon 2 of 5	ENSP00000489900.1	A0A1B0GTZ4
DCLK3	ENST00000929032.1		c.1471G>C	p.Glu491Gln	missense	Exon 2 of 4	ENSP00000599091.1
DCLK3	ENST00000416516.2	TSL:5	c.964G>C	p.Glu322Gln	missense	Exon 2 of 5	ENSP00000394484.2	Q9C098

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461492

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727062

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33386

American (AMR)

AF:

0.00

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111914

Other (OTH)

AF:

0.00

AC:

AN:

60370

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

0.096

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.72

M_CAP

Benign

0.022

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.0

PhyloP100

1.8

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

REVEL

Benign

0.14

Sift

Uncertain

0.0040

Sift4G

Benign

0.15

Polyphen

0.95

Vest4

0.15

MutPred

0.17

Gain of glycosylation at T327 (P = 0.0087)

MVP

0.78

MPC

0.23

ClinPred

0.56

GERP RS

4.7

Varity_R

0.20

gMVP

0.30

Mutation Taster

=95/5

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over