rs10489286

Positions:

• chr1-172343779-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015569.5(DNM3):​c.1893+20439G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,046 control chromosomes in the GnomAD database, including 2,121 homozygotes. 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: 𝑓 0.15 (2121 hom., cov: 32)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528

Genes affected

DNM3 (HGNC:29125): (dynamin 3) This gene encodes a member of a family of guanosine triphosphate (GTP)-binding proteins that associate with microtubules and are involved in vesicular transport. The encoded protein functions in the development of megakaryocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1893+20439G>A		intron_variant		ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1893+20439G>A		intron_variant		1	NM_015569.5	ENSP00000486701	A1
DNM3	ENST00000367731.5	c.1881+34940G>A		intron_variant		1		ENSP00000356705	P3
DNM3	ENST00000485254.3	c.1911+34940G>A		intron_variant		1		ENSP00000429165
DNM3	ENST00000355305.9	c.1911+34940G>A		intron_variant		5		ENSP00000347457	A1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22648 AN: 151928 Hom.: 2121 Cov.: 32

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.149 AC: 22658 AN: 152046 Hom.: 2121 Cov.: 32 AF XY: 0.149 AC XY: 11098 AN XY: 74282

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.141

Alfa AF: 0.183 Hom.: 1700

Bravo AF: 0.134

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.87

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: rs10489286; hg19: chr1-172312919;