chr3-36737710-T-C

Variant names:

• chr3-36737710-T-C
• NM_001394672.2:c.1457A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394672.2(DCLK3):​c.1457A>G​(p.Gln486Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCLK3 NM_001394672.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.197

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052631468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK3	NM_001394672.2	c.1457A>G	p.Gln486Arg	missense_variant	Exon 2 of 5	ENST00000636136.2	NP_001381601.1
DCLK3	NM_033403.1	c.950A>G	p.Gln317Arg	missense_variant	Exon 2 of 5		NP_208382.1
DCLK3	XM_047449090.1	c.1457A>G	p.Gln486Arg	missense_variant	Exon 2 of 4		XP_047305046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK3	ENST00000636136.2	c.1457A>G	p.Gln486Arg	missense_variant	Exon 2 of 5	5	NM_001394672.2	ENSP00000489900.1
DCLK3	ENST00000416516.2	c.950A>G	p.Gln317Arg	missense_variant	Exon 2 of 5	5		ENSP00000394484.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.950A>G (p.Q317R) alteration is located in exon 2 (coding exon 1) of the DCLK3 gene. This alteration results from a A to G substitution at nucleotide position 950, causing the glutamine (Q) at amino acid position 317 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
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.4
DANN	Benign	0.90
DEOGEN2	Benign	0.0097	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.39	N;.
REVEL	Benign	0.031
Sift	Benign	0.16	T;.
Sift4G	Benign	0.52	T;.
Polyphen		0.0020	B;.
Vest4		0.047
MutPred		0.22		Gain of glycosylation at T312 (P = 0.0012);.;
MVP		0.52
MPC		0.22
ClinPred		0.036	T
GERP RS		-2.3
Varity_R		0.10
gMVP		0.16

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: chr3-36779201;