rs568300

Variant names:

• chr9-35093023-T-C
• rs568300
• NM_032634.4:c.1119+7A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-35093023-T-C
• chr9-35093023-T-A
• chr9-35093023-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032634.4(PIGO):​c.1119+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,596,962 control chromosomes in the GnomAD database, including 239,260 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20960 hom., cov: 33)
  • Exomes 𝑓: 0.55 (218300 hom.)
• Consequence: PIGO NM_032634.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002062
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.511
• Publications: 17 publications found

Genes affected

PIGO (HGNC:23215): (phosphatidylinositol glycan anchor biosynthesis class O) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid which contains three mannose molecules in its core backbone. The GPI-anchor is found on many blood cells and serves to anchor proteins to the cell surface. This protein is involved in the transfer of ethanolaminephosphate (EtNP) to the third mannose in GPI. At least three alternatively spliced transcripts encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

PIGO Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hyperphosphatasia with intellectual disability syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina
• hyperphosphatasia-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-35093023-T-C is Benign according to our data. Variant chr9-35093023-T-C is described in ClinVar as Benign. ClinVar VariationId is 262093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032634.4. 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
	PIGO	NM_032634.4	MANE Select	c.1119+7A>G		splice_region intron	N/A	NP_116023.2
	PIGO	NM_001201484.2		c.1119+7A>G		splice_region intron	N/A	NP_001188413.1	Q8TEQ8-2
	PIGO	NM_152850.4		c.1119+7A>G		splice_region intron	N/A	NP_690577.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGO	ENST00000378617.4	TSL:1 MANE Select	c.1119+7A>G		splice_region intron	N/A	ENSP00000367880.3	Q8TEQ8-1
	PIGO	ENST00000298004.9	TSL:1	c.1119+7A>G		splice_region intron	N/A	ENSP00000298004.5	Q8TEQ8-2
	PIGO	ENST00000907113.1		c.1119+7A>G		splice_region intron	N/A	ENSP00000577172.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79111 AN: 151972 Hom.: 20955 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.531

GnomAD2 exomes AF: 0.546 AC: 135034 AN: 247180 AF XY: 0.544

Gnomad AFR exome AF: 0.425

Gnomad AMR exome AF: 0.672

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.372

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.575

GnomAD4 exome AF: 0.547 AC: 790016 AN: 1444870 Hom.: 218300 Cov.: 51 AF XY: 0.546 AC XY: 390847 AN XY: 715278

African (AFR) AF: 0.432 AC: 14299 AN: 33112

American (AMR) AF: 0.664 AC: 29136 AN: 43862

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 12786 AN: 25776

East Asian (EAS) AF: 0.425 AC: 16673 AN: 39228

South Asian (SAS) AF: 0.480 AC: 41079 AN: 85586

European-Finnish (FIN) AF: 0.597 AC: 31754 AN: 53162

Middle Eastern (MID) AF: 0.517 AC: 2935 AN: 5682

European-Non Finnish (NFE) AF: 0.555 AC: 609987 AN: 1099006

Other (OTH) AF: 0.528 AC: 31367 AN: 59456

GnomAD4 genome AF: 0.520 AC: 79134 AN: 152092 Hom.: 20960 Cov.: 33 AF XY: 0.521 AC XY: 38699 AN XY: 74334

African (AFR) AF: 0.431 AC: 17862 AN: 41478

American (AMR) AF: 0.578 AC: 8845 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1734 AN: 3468

East Asian (EAS) AF: 0.379 AC: 1960 AN: 5166

South Asian (SAS) AF: 0.468 AC: 2257 AN: 4824

European-Finnish (FIN) AF: 0.606 AC: 6411 AN: 10586

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.565 AC: 38408 AN: 67960

Other (OTH) AF: 0.526 AC: 1111 AN: 2114

Alfa AF: 0.539 Hom.: 22012

Bravo AF: 0.519

Asia WGS AF: 0.422 AC: 1469 AN: 3478

EpiCase AF: 0.564

EpiControl AF: 0.564

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hyperphosphatasia with intellectual disability syndrome 2 (3)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.73
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.0020
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: rs568300; hg19: chr9-35093020; COSMIC: COSV53052867; COSMIC: COSV53052867;