rs17714063

Variant names:

• chr18-62101142-A-G
• rs17714063
• NM_176787.5:c.2010T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-62101142-A-G
• chr18-62101142-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001438896.1(PIGN):​c.2010T>C​(p.Thr670Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,606,734 control chromosomes in the GnomAD database, including 42,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2942 hom., cov: 32)
  • Exomes 𝑓: 0.22 (40034 hom.)
• Consequence: PIGN NM_001438896.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0560
• Publications: 16 publications found

Genes affected

PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]

PIGN Gene-Disease associations (from GenCC):

• multiple congenital anomalies-hypotonia-seizures syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen, PanelApp Australia
• Fryns syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 18-62101142-A-G is Benign according to our data. Variant chr18-62101142-A-G is described in ClinVar as Benign. ClinVar VariationId is 403300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.056 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438896.1. 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
	PIGN	NM_176787.5	MANE Select	c.2010T>C	p.Thr670Thr	synonymous	Exon 22 of 31	NP_789744.1
	PIGN	NM_001438896.1		c.2010T>C	p.Thr670Thr	synonymous	Exon 22 of 32	NP_001425825.1
	PIGN	NM_012327.6		c.2010T>C	p.Thr670Thr	synonymous	Exon 21 of 30	NP_036459.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGN	ENST00000640252.2	TSL:1 MANE Select	c.2010T>C	p.Thr670Thr	synonymous	Exon 22 of 31	ENSP00000492233.1
	PIGN	ENST00000400334.7	TSL:1	c.2010T>C	p.Thr670Thr	synonymous	Exon 21 of 30	ENSP00000383188.2
	PIGN	ENST00000638424.1	TSL:5	n.2010T>C		non_coding_transcript_exon	Exon 20 of 29	ENSP00000491963.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25948 AN: 152082 Hom.: 2941 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.178 AC: 43967 AN: 247562 AF XY: 0.181

Gnomad AFR exome AF: 0.0465

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.255

Gnomad EAS exome AF: 0.00279

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.224 AC: 326540 AN: 1454534 Hom.: 40034 Cov.: 30 AF XY: 0.223 AC XY: 161168 AN XY: 724040

African (AFR) AF: 0.0424 AC: 1417 AN: 33428

American (AMR) AF: 0.114 AC: 5085 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6493 AN: 26078

East Asian (EAS) AF: 0.00141 AC: 56 AN: 39632

South Asian (SAS) AF: 0.114 AC: 9848 AN: 86122

European-Finnish (FIN) AF: 0.237 AC: 12470 AN: 52718

Middle Eastern (MID) AF: 0.243 AC: 1395 AN: 5748

European-Non Finnish (NFE) AF: 0.251 AC: 277270 AN: 1106006

Other (OTH) AF: 0.208 AC: 12506 AN: 60122

GnomAD4 genome AF: 0.171 AC: 25954 AN: 152200 Hom.: 2942 Cov.: 32 AF XY: 0.168 AC XY: 12469 AN XY: 74404

African (AFR) AF: 0.0496 AC: 2059 AN: 41548

American (AMR) AF: 0.152 AC: 2327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3472

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5186

South Asian (SAS) AF: 0.107 AC: 518 AN: 4824

European-Finnish (FIN) AF: 0.245 AC: 2589 AN: 10588

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16843 AN: 67980

Other (OTH) AF: 0.195 AC: 411 AN: 2106

Alfa AF: 0.225 Hom.: 2247

Bravo AF: 0.159

Asia WGS AF: 0.0810 AC: 284 AN: 3478

EpiCase AF: 0.252

EpiControl AF: 0.252

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Multiple congenital anomalies-hypotonia-seizures syndrome 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.4
DANN	Benign	0.75
PhyloP100		-0.056
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: rs17714063; hg19: chr18-59768375;