3-36737653-C-T

Variant names:

• chr3-36737653-C-T
• rs202070330
• NM_001394672.2:c.1514G>A

Variant summary

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

The NM_001394672.2(DCLK3):​c.1514G>A​(p.Arg505Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: DCLK3 NM_001394672.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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 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=0.07639828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK3	NM_001394672.2	c.1514G>A	p.Arg505Gln	missense_variant	Exon 2 of 5	ENST00000636136.2	NP_001381601.1
DCLK3	NM_033403.1	c.1007G>A	p.Arg336Gln	missense_variant	Exon 2 of 5		NP_208382.1
DCLK3	XM_047449090.1	c.1514G>A	p.Arg505Gln	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.1514G>A	p.Arg505Gln	missense_variant	Exon 2 of 5	5	NM_001394672.2	ENSP00000489900.1
DCLK3	ENST00000416516.2	c.1007G>A	p.Arg336Gln	missense_variant	Exon 2 of 5	5		ENSP00000394484.2

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 54 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000370 AC: 92 AN: 248574 Hom.: 0 AF XY: 0.000393 AC XY: 53 AN XY: 134820

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000621

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.000383 AC: 560 AN: 1461488 Hom.: 0 Cov.: 30 AF XY: 0.000387 AC XY: 281 AN XY: 727026

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000380

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000454

Gnomad4 OTH exome AF: 0.000497

GnomAD4 genome AF: 0.000354 AC: 54 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24 AN XY: 74498

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000514

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000483 Hom.: 0

Bravo AF: 0.000389

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000478 AC: 4

ExAC AF: 0.000314 AC: 38

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1007G>A (p.R336Q) alteration is located in exon 2 (coding exon 1) of the DCLK3 gene. This alteration results from a G to A substitution at nucleotide position 1007, causing the arginine (R) at amino acid position 336 to be replaced by a glutamine (Q). 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	0.090
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.015
Eigen_PC	Benign	-0.021
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.78	T;T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.93	N;.
REVEL	Benign	0.14
Sift	Benign	0.14	T;.
Sift4G	Benign	0.52	T;.
Polyphen		0.99	D;.
Vest4		0.17
MVP		0.82
MPC		0.25
ClinPred		0.056	T
GERP RS		5.4
Varity_R		0.057
gMVP		0.32

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: rs202070330; hg19: chr3-36779144;