rs756116672

Variant names:

• chr3-36737696-C-A
• rs756116672
• NM_001394672.2:c.1471G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-36737696-C-A
• chr3-36737696-C-G
• chr3-36737696-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394672.2(DCLK3):​c.1471G>T​(p.Glu491*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DCLK3 NM_001394672.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1471G>T	p.Glu491*	stop_gained	Exon 2 of 5	NP_001381601.1	A0A1B0GTZ4
	DCLK3	NM_033403.1		c.964G>T	p.Glu322*	stop_gained	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.1471G>T	p.Glu491*	stop_gained	Exon 2 of 5	ENSP00000489900.1	A0A1B0GTZ4
	DCLK3	ENST00000929032.1		c.1471G>T	p.Glu491*	stop_gained	Exon 2 of 4	ENSP00000599091.1
	DCLK3	ENST00000416516.2	TSL:5	c.964G>T	p.Glu322*	stop_gained	Exon 2 of 5	ENSP00000394484.2	Q9C098

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461492 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727062

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111914

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.90	D
PhyloP100		1.8
Vest4		0.20
GERP RS		4.7
Mutation Taster		=23/177	disease causing (fs/PTC)

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: rs756116672; hg19: chr3-36779187;