rs12411264

Variant names:

• chr1-172224528-G-A
• rs12411264
• NM_015569.5:c.1660-29045G>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.1660-29045G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,840 control chromosomes in the GnomAD database, including 2,476 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 0.17 (2476 hom., cov: 31)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1660-29045G>A		intron_variant	Intron 14 of 20	ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1660-29045G>A		intron_variant	Intron 14 of 20	1	NM_015569.5	ENSP00000486701.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25184 AN: 151722 Hom.: 2472 Cov.: 31

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.166 AC: 25208 AN: 151840 Hom.: 2476 Cov.: 31 AF XY: 0.165 AC XY: 12245 AN XY: 74182

African (AFR) AF: 0.0556 AC: 2306 AN: 41442

American (AMR) AF: 0.192 AC: 2922 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1440 AN: 5136

South Asian (SAS) AF: 0.183 AC: 880 AN: 4802

European-Finnish (FIN) AF: 0.189 AC: 1989 AN: 10510

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.213 AC: 14447 AN: 67918

Other (OTH) AF: 0.175 AC: 368 AN: 2108

Alfa AF: 0.168 Hom.: 488

Bravo AF: 0.164

Asia WGS AF: 0.211 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.73
PhyloP100		-0.58
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: rs12411264; hg19: chr1-172193668;