rs1023479

chr1-172385992-G-Achr1-172385992-G-Cchr1-172385992-G-T

Variant summary

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

The NM_015569.5(DNM3):c.2059-1141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,142 control chromosomes in the GnomAD database, including 40,542 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 0.70 (40542 hom., cov: 32)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

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:8960): (phosphatidylinositol glycan anchor biosynthesis class C) This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI) lipid anchor biosynthesis. The GPI lipid anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. The encoded protein is one subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. Two alternatively spliced transcripts that encode the same protein have been found for this gene. A pseudogene on chromosome 11 has also been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM3	NM_015569.5	c.2059-1141G>A		intron_variant		ENST00000627582.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM3	ENST00000627582.3	c.2059-1141G>A		intron_variant		1	NM_015569.5	A1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106680 AN: 152024 Hom.: 40513 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.702 AC: 106744 AN: 152142 Hom.: 40542 Cov.: 32 AF XY: 0.705 AC XY: 52441 AN XY: 74360

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.743

Alfa AF: 0.814 Hom.: 98703

Bravo AF: 0.689

Asia WGS AF: 0.815 AC: 2832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	6.3
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: rs1023479; hg19: chr1-172355132;