rs1011731

Positions:

• chr1-172377408-G-A
• chr1-172377408-G-C

Variant summary

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

The NM_015569.5(DNM3):​c.1894-1610G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,204 control chromosomes in the GnomAD database, including 20,186 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 0.48 (20186 hom., cov: 29)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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]

PIGC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1894-1610G>A		intron_variant		ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1894-1610G>A		intron_variant		1	NM_015569.5	ENSP00000486701.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 71814 AN: 151088 Hom.: 20184 Cov.: 29

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.475 AC: 71832 AN: 151204 Hom.: 20186 Cov.: 29 AF XY: 0.482 AC XY: 35577 AN XY: 73858

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.533

Alfa AF: 0.574 Hom.: 56120

Bravo AF: 0.470

Asia WGS AF: 0.694 AC: 2405 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.65

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: rs1011731; hg19: chr1-172346548;