rs1023479

Variant names:

• chr1-172385992-G-A
• rs1023479
• NM_015569.5:c.2059-1141G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-172385992-G-A
• chr1-172385992-G-C
• chr1-172385992-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350204.2(DNM3):​c.2077-1141G>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_001350204.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 12 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350204.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM3	NM_015569.5	MANE Select	c.2059-1141G>A		intron	N/A	NP_056384.2
	DNM3	NM_001350204.2		c.2077-1141G>A		intron	N/A	NP_001337133.1
	DNM3	NM_001136127.3		c.2047-1141G>A		intron	N/A	NP_001129599.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM3	ENST00000627582.3	TSL:1 MANE Select	c.2059-1141G>A		intron	N/A	ENSP00000486701.1
	DNM3	ENST00000367731.5	TSL:1	c.2047-1141G>A		intron	N/A	ENSP00000356705.1
	DNM3	ENST00000485254.3	TSL:1	c.2077-1141G>A		intron	N/A	ENSP00000429165.2

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

African (AFR) AF: 0.382 AC: 15845 AN: 41472

American (AMR) AF: 0.808 AC: 12357 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2743 AN: 3472

East Asian (EAS) AF: 0.876 AC: 4534 AN: 5176

South Asian (SAS) AF: 0.784 AC: 3778 AN: 4820

European-Finnish (FIN) AF: 0.802 AC: 8479 AN: 10578

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56478 AN: 68002

Other (OTH) AF: 0.743 AC: 1573 AN: 2116

Alfa AF: 0.795 Hom.: 204984

Bravo AF: 0.689

Asia WGS AF: 0.815 AC: 2832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.3
DANN	Benign	0.65
PhyloP100		0.55
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: rs1023479; hg19: chr1-172355132;