rs12075079

Positions:

• chr1-172250855-A-G
• chr1-172250855-A-T

Variant summary

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

The ENST00000627582.3(DNM3):​c.1660-2718A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,064 control chromosomes in the GnomAD database, including 2,427 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 (2427 hom., cov: 32)
• Consequence: DNM3 ENST00000627582.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1660-2718A>G		intron_variant		ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1660-2718A>G		intron_variant		1	NM_015569.5	ENSP00000486701	A1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25088 AN: 151946 Hom.: 2423 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.153

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: 0.165 AC: 25112 AN: 152064 Hom.: 2427 Cov.: 32 AF XY: 0.164 AC XY: 12162 AN XY: 74324

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.175

Alfa AF: 0.197 Hom.: 1553

Bravo AF: 0.164

Asia WGS AF: 0.205 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.82

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: rs12075079; hg19: chr1-172219995;