rs477289

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1660-31319A>C		intron_variant		ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1660-31319A>C		intron_variant		1	NM_015569.5	ENSP00000486701	A1

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

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.337

Alfa AF: 0.276 Hom.: 5754

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

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: rs477289; hg19: chr1-172191394;