3-36737632-C-A

Variant names:

• chr3-36737632-C-A
• rs756277470
• NM_001394672.2:c.1535G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394672.2(DCLK3):​c.1535G>T​(p.Arg512Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R512Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCLK3 NM_001394672.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36313117).

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.1535G>T	p.Arg512Leu	missense	Exon 2 of 5	NP_001381601.1	A0A1B0GTZ4
	DCLK3	NM_033403.1		c.1028G>T	p.Arg343Leu	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.1535G>T	p.Arg512Leu	missense	Exon 2 of 5	ENSP00000489900.1	A0A1B0GTZ4
	DCLK3	ENST00000929032.1		c.1535G>T	p.Arg512Leu	missense	Exon 2 of 4	ENSP00000599091.1
	DCLK3	ENST00000416516.2	TSL:5	c.1028G>T	p.Arg343Leu	missense	Exon 2 of 5	ENSP00000394484.2	Q9C098

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461726 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727150

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.5
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.076	T
Polyphen		1.0	D
Vest4		0.64
MutPred		0.39		Loss of MoRF binding (P = 0.0097)
MVP		0.84
MPC		0.39
ClinPred		0.65	D
GERP RS		5.6
Varity_R		0.26
gMVP		0.52
Mutation Taster		=92/8	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: rs756277470; hg19: chr3-36779123; COSMIC: COSV69363021;