rs756277470

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-36737632-C-A
• chr3-36737632-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK3	NM_001394672.2	c.1535G>T	p.Arg512Leu	missense_variant	Exon 2 of 5	ENST00000636136.2	NP_001381601.1
DCLK3	NM_033403.1	c.1028G>T	p.Arg343Leu	missense_variant	Exon 2 of 5		NP_208382.1
DCLK3	XM_047449090.1	c.1535G>T	p.Arg512Leu	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.1535G>T	p.Arg512Leu	missense_variant	Exon 2 of 5	5	NM_001394672.2	ENSP00000489900.1
DCLK3	ENST00000416516.2	c.1028G>T	p.Arg343Leu	missense_variant	Exon 2 of 5	5		ENSP00000394484.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.1	L;.
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

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: chr3-36779123; COSMIC: COSV69363021;