rs10489286

Variant names:

• chr1-172343779-G-A
• rs10489286
• NM_015569.5:c.1893+20439G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015569.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM3	NM_015569.5	MANE Select	c.1893+20439G>A		intron	N/A	NP_056384.2
	DNM3	NM_001350204.2		c.1911+34940G>A		intron	N/A	NP_001337133.1
	DNM3	NM_001136127.3		c.1881+34940G>A		intron	N/A	NP_001129599.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM3	ENST00000627582.3	TSL:1 MANE Select	c.1893+20439G>A		intron	N/A	ENSP00000486701.1
	DNM3	ENST00000367731.5	TSL:1	c.1881+34940G>A		intron	N/A	ENSP00000356705.1
	DNM3	ENST00000485254.3	TSL:1	c.1911+34940G>A		intron	N/A	ENSP00000429165.2

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

African (AFR) AF: 0.0631 AC: 2617 AN: 41496

American (AMR) AF: 0.124 AC: 1892 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3468

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5180

South Asian (SAS) AF: 0.115 AC: 555 AN: 4822

European-Finnish (FIN) AF: 0.268 AC: 2822 AN: 10518

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.205 AC: 13947 AN: 67986

Other (OTH) AF: 0.141 AC: 298 AN: 2112

Alfa AF: 0.184 Hom.: 2421

Bravo AF: 0.134

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs10489286; hg19: chr1-172312919;