chr3-36737710-T-G

Position:

• chr3-36737710-T-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>C​(p.Gln486Pro) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q486R) has been classified 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=0.056262434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLK3	NM_001394672.2	c.1457A>C	p.Gln486Pro	missense_variant	2/5	ENST00000636136.2
DCLK3	NM_033403.1	c.950A>C	p.Gln317Pro	missense_variant	2/5
DCLK3	XM_047449090.1	c.1457A>C	p.Gln486Pro	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLK3	ENST00000636136.2	c.1457A>C	p.Gln486Pro	missense_variant	2/5	5	NM_001394672.2	P1
DCLK3	ENST00000416516.2	c.950A>C	p.Gln317Pro	missense_variant	2/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 20, 2023

The c.950A>C (p.Q317P) alteration is located in exon 2 (coding exon 1) of the DCLK3 gene. This alteration results from a A to C substitution at nucleotide position 950, causing the glutamine (Q) at amino acid position 317 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	0.064
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.5
DANN	Benign	0.23
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.47	N;.
REVEL	Benign	0.082
Sift	Benign	0.48	T;.
Sift4G	Benign	0.30	T;.
Polyphen		0.0	B;.
Vest4		0.066
MutPred		0.33		Gain of glycosylation at T312 (P = 0.0012);.;
MVP		0.51
MPC		0.25
ClinPred		0.023	T
GERP RS		-2.3
Varity_R		0.13
gMVP		0.24

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

Other links and lift over

dbSNP: rs1701283561; hg19: chr3-36779201;