rs1011731

Variant names:

• chr1-172377408-G-A
• rs1011731
• NM_015569.5:c.1894-1610G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 75 publications found

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]

PIGC Gene-Disease associations (from GenCC):

• glycosylphosphatidylinositol biosynthesis defect 16

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1894-1610G>A		intron_variant	Intron 17 of 20	ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1894-1610G>A		intron_variant	Intron 17 of 20	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

African (AFR) AF: 0.162 AC: 6664 AN: 41202

American (AMR) AF: 0.634 AC: 9609 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1915 AN: 3462

East Asian (EAS) AF: 0.871 AC: 4469 AN: 5132

South Asian (SAS) AF: 0.565 AC: 2711 AN: 4798

European-Finnish (FIN) AF: 0.549 AC: 5708 AN: 10396

Middle Eastern (MID) AF: 0.587 AC: 169 AN: 288

European-Non Finnish (NFE) AF: 0.574 AC: 38875 AN: 67770

Other (OTH) AF: 0.533 AC: 1121 AN: 2102

Alfa AF: 0.555 Hom.: 107521

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
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1011731; hg19: chr1-172346548;