rs4916251

Positions:

• chr1-172377256-T-A

Variant summary

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

The NM_015569.5(DNM3):​c.1894-1762T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,482 control chromosomes in the GnomAD database, including 40,621 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 0.71 (40621 hom., cov: 29)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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=-0.89).
• 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	Protein	UniProt
DNM3	NM_015569.5	c.1894-1762T>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.1894-1762T>A		intron_variant		1	NM_015569.5	ENSP00000486701	A1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 106754 AN: 151364 Hom.: 40592 Cov.: 29

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.705 AC: 106820 AN: 151482 Hom.: 40621 Cov.: 29 AF XY: 0.708 AC XY: 52421 AN XY: 74012

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.746

Alfa AF: 0.756 Hom.: 5673

Bravo AF: 0.693

Asia WGS AF: 0.818 AC: 2841 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.61

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: rs4916251; hg19: chr1-172346396;