1-172371777-C-G

Variant names:

• chr1-172371777-C-G
• rs991790
• NM_015569.5:c.1894-7241C>G

Variant summary

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

The NM_015569.5(DNM3):​c.1894-7241C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,674 control chromosomes in the GnomAD database, including 20,096 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 0.47 (20096 hom., cov: 31)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572
• Publications: 5 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=-0.8).
• 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.1894-7241C>G		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.1894-7241C>G		intron_variant	Intron 17 of 20	1	NM_015569.5	ENSP00000486701.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71475 AN: 151558 Hom.: 20094 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.471 AC: 71491 AN: 151674 Hom.: 20096 Cov.: 31 AF XY: 0.477 AC XY: 35356 AN XY: 74056

African (AFR) AF: 0.153 AC: 6338 AN: 41432

American (AMR) AF: 0.631 AC: 9605 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1918 AN: 3460

East Asian (EAS) AF: 0.870 AC: 4479 AN: 5148

South Asian (SAS) AF: 0.562 AC: 2704 AN: 4808

European-Finnish (FIN) AF: 0.547 AC: 5711 AN: 10444

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38858 AN: 67836

Other (OTH) AF: 0.528 AC: 1117 AN: 2114

Alfa AF: 0.364 Hom.: 1107

Bravo AF: 0.467

Asia WGS AF: 0.694 AC: 2410 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.69
PhyloP100		0.57
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: rs991790; hg19: chr1-172340917; COSMIC: COSV62465910; COSMIC: COSV62465910;