rs477289

Variant names:

• chr1-172222254-A-C
• rs477289
• NM_015569.5:c.1660-31319A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-172222254-A-C
• chr1-172222254-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015569.5(DNM3):​c.1660-31319A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,058 control chromosomes in the GnomAD database, including 10,953 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 0.35 (10953 hom., cov: 32)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 5 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1660-31319A>C		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.1660-31319A>C		intron_variant	Intron 14 of 20	1	NM_015569.5	ENSP00000486701.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53448 AN: 151938 Hom.: 10909 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.352 AC: 53568 AN: 152058 Hom.: 10953 Cov.: 32 AF XY: 0.349 AC XY: 25941 AN XY: 74332

African (AFR) AF: 0.573 AC: 23781 AN: 41468

American (AMR) AF: 0.283 AC: 4317 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1774 AN: 5162

South Asian (SAS) AF: 0.293 AC: 1412 AN: 4820

European-Finnish (FIN) AF: 0.256 AC: 2708 AN: 10586

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17541 AN: 67964

Other (OTH) AF: 0.337 AC: 712 AN: 2114

Alfa AF: 0.289 Hom.: 8636

Bravo AF: 0.365

Asia WGS AF: 0.358 AC: 1246 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.9
DANN	Benign	0.73
PhyloP100		-1.8
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: rs477289; hg19: chr1-172191394;