chr1-172393809-G-T

Variant names:

• chr1-172393809-G-T
• rs3768445
• ENST00000484368.1:n.986C>A

Variant summary

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

The ENST00000484368.1(PIGC):​n.986C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,462 control chromosomes in the GnomAD database, including 40,778 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 (40649 hom., cov: 32)
  • Exomes 𝑓: 0.78 (129 hom.)
• Consequence: PIGC ENST00000484368.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 3 publications found

Genes affected

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]

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]

LOC102724528 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000484368.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM3	NM_015569.5	MANE Select	c.2522+5000G>T		intron	N/A	NP_056384.2
	DNM3	NM_001350204.2		c.2540+5000G>T		intron	N/A	NP_001337133.1
	DNM3	NM_001136127.3		c.2510+5000G>T		intron	N/A	NP_001129599.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGC	ENST00000484368.1	TSL:1	n.986C>A		non_coding_transcript_exon	Exon 5 of 5
	DNM3	ENST00000627582.3	TSL:1 MANE Select	c.2522+5000G>T		intron	N/A	ENSP00000486701.1
	DNM3	ENST00000367731.5	TSL:1	c.2510+5000G>T		intron	N/A	ENSP00000356705.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106861 AN: 151904 Hom.: 40618 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.775 AC: 341 AN: 440 Hom.: 129 Cov.: 0 AF XY: 0.771 AC XY: 202 AN XY: 262

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.772 AC: 329 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.875 AC: 7 AN: 8

Other (OTH) AF: 0.833 AC: 5 AN: 6

GnomAD4 genome AF: 0.703 AC: 106931 AN: 152022 Hom.: 40649 Cov.: 32 AF XY: 0.707 AC XY: 52516 AN XY: 74310

African (AFR) AF: 0.387 AC: 16020 AN: 41408

American (AMR) AF: 0.809 AC: 12367 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2744 AN: 3470

East Asian (EAS) AF: 0.875 AC: 4531 AN: 5176

South Asian (SAS) AF: 0.784 AC: 3781 AN: 4820

European-Finnish (FIN) AF: 0.802 AC: 8462 AN: 10556

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

European-Non Finnish (NFE) AF: 0.831 AC: 56500 AN: 67980

Other (OTH) AF: 0.742 AC: 1569 AN: 2114

Alfa AF: 0.776 Hom.: 60357

Bravo AF: 0.691

Asia WGS AF: 0.811 AC: 2820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.29
PhyloP100		0.0
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: rs3768445; hg19: chr1-172362949;