rs1048575

Positions:

• chr1-77092372-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005482.3(PIGK):​c.*2C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,326,028 control chromosomes in the GnomAD database, including 50,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7584 hom., cov: 32)
  • Exomes 𝑓: 0.26 (42709 hom.)
• Consequence: PIGK NM_005482.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.305

Genes affected

PIGK (HGNC:8965): (phosphatidylinositol glycan anchor biosynthesis class K) This gene encodes a member of the cysteine protease family C13 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 a member of the multisubunit enzyme, GPI transamidase and is thought to be its enzymatic component. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-77092372-G-C is Benign according to our data. Variant chr1-77092372-G-C is described in ClinVar as [Benign]. Clinvar id is 1327022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGK	NM_005482.3	c.*2C>G		3_prime_UTR_variant	11/11	ENST00000370812.8	NP_005473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGK	ENST00000370812	c.*2C>G		3_prime_UTR_variant	11/11	1	NM_005482.3	ENSP00000359848.3
PIGK	ENST00000445065.5	c.*2C>G		3_prime_UTR_variant	8/8	1		ENSP00000388854.1
PIGK	ENST00000487906.5	n.*679C>G		non_coding_transcript_exon_variant	7/7	5		ENSP00000474518.1
PIGK	ENST00000487906.5	n.*679C>G		3_prime_UTR_variant	7/7	5		ENSP00000474518.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45999 AN: 151682 Hom.: 7580 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.320

GnomAD3 exomes AF: 0.291 AC: 67119 AN: 230462 Hom.: 10565 AF XY: 0.283 AC XY: 35256 AN XY: 124756

Gnomad AFR exome AF: 0.414

Gnomad AMR exome AF: 0.420

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.406

Gnomad SAS exome AF: 0.287

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.263 AC: 308269 AN: 1174228 Hom.: 42709 Cov.: 16 AF XY: 0.261 AC XY: 156080 AN XY: 596972

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.412

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.303 AC: 46014 AN: 151800 Hom.: 7584 Cov.: 32 AF XY: 0.303 AC XY: 22453 AN XY: 74186

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.316

Alfa AF: 0.256 Hom.: 1765

Bravo AF: 0.324

Asia WGS AF: 0.305 AC: 1060 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs1048575; hg19: chr1-77558057; COSMIC: COSV63650106;