chr1-77092372-G-C

Variant names:

• chr1-77092372-G-C
• rs1048575
• NM_005482.3:c.*2C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

PIGK Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005482.3. 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
	PIGK	NM_005482.3	MANE Select	c.*2C>G		3_prime_UTR	Exon 11 of 11	NP_005473.1	Q92643-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGK	ENST00000370812.8	TSL:1 MANE Select	c.*2C>G		3_prime_UTR	Exon 11 of 11	ENSP00000359848.3	Q92643-1
	PIGK	ENST00000445065.5	TSL:1	c.*2C>G		3_prime_UTR	Exon 8 of 8	ENSP00000388854.1	B1AK81
	PIGK	ENST00000858231.1		c.*2C>G		3_prime_UTR	Exon 12 of 12	ENSP00000528290.1

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

GnomAD2 exomes AF: 0.291 AC: 67119 AN: 230462 AF XY: 0.283

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 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

African (AFR) AF: 0.420 AC: 11311 AN: 26916

American (AMR) AF: 0.412 AC: 15769 AN: 38256

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 6883 AN: 23820

East Asian (EAS) AF: 0.386 AC: 14555 AN: 37672

South Asian (SAS) AF: 0.288 AC: 21624 AN: 74988

European-Finnish (FIN) AF: 0.196 AC: 10413 AN: 53070

Middle Eastern (MID) AF: 0.313 AC: 1616 AN: 5170

European-Non Finnish (NFE) AF: 0.246 AC: 212113 AN: 863744

Other (OTH) AF: 0.276 AC: 13985 AN: 50592

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

African (AFR) AF: 0.413 AC: 17104 AN: 41400

American (AMR) AF: 0.364 AC: 5552 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2082 AN: 5170

South Asian (SAS) AF: 0.279 AC: 1341 AN: 4802

European-Finnish (FIN) AF: 0.184 AC: 1937 AN: 10516

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16048 AN: 67882

Other (OTH) AF: 0.316 AC: 667 AN: 2112

Alfa AF: 0.256 Hom.: 1765

Bravo AF: 0.324

Asia WGS AF: 0.305 AC: 1060 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.60
PhyloP100		0.30
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: rs1048575; hg19: chr1-77558057; COSMIC: COSV63650106;