chr3-36737653-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. 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. 15/22 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
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07639828).

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.1514G>A	p.Arg505Gln	missense	Exon 2 of 5	NP_001381601.1	A0A1B0GTZ4
	DCLK3	NM_033403.1		c.1007G>A	p.Arg336Gln	missense	Exon 2 of 5	NP_208382.1	Q9C098

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK3	ENST00000636136.2	TSL:5 MANE Select	c.1514G>A	p.Arg505Gln	missense	Exon 2 of 5	ENSP00000489900.1	A0A1B0GTZ4
	DCLK3	ENST00000929032.1		c.1514G>A	p.Arg505Gln	missense	Exon 2 of 4	ENSP00000599091.1
	DCLK3	ENST00000416516.2	TSL:5	c.1007G>A	p.Arg336Gln	missense	Exon 2 of 5	ENSP00000394484.2	Q9C098

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

GnomAD2 exomes AF: 0.000370 AC: 92 AN: 248574 AF XY: 0.000393

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 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

African (AFR) AF: 0.0000299 AC: 1 AN: 33452

American (AMR) AF: 0.000380 AC: 17 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.000454 AC: 505 AN: 1111854

Other (OTH) AF: 0.000497 AC: 30 AN: 60382

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

African (AFR) AF: 0.000144 AC: 6 AN: 41576

American (AMR) AF: 0.000719 AC: 11 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000514 AC: 35 AN: 68038

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000487 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
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
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs202070330; hg19: chr3-36779144;