rs587776528

Variant names:

• chr1-160032009-G-C
• rs587776528
• ENST00000509700.2:c.669+9825C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-160032009-G-C
• chr1-160032009-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000772608.1(ENSG00000300536):​n.313G>C variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000248 in 403,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: ENSG00000300536 ENST00000772608.1 non_coding_transcript_exon
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:1
• Conservation: PhyloP100: 3.87
• Publications: 5 publications found

Genes affected

KCNJ10 (HGNC:6256): (potassium inwardly rectifying channel subfamily J member 10) This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]

ENSG00000300536 (HGNC:):

PIGM (HGNC:18858): (phosphatidylinositol glycan anchor biosynthesis class M) This gene encodes a transmembrane protein that is located in the endoplasmic reticulum and is involved in GPI-anchor biosynthesis. The glycosylphosphatidylinositol (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 gene encodes a mannosyltransferase, GPI-MT-I, that transfers the first mannose to GPI on the lumenal side of the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

PIGM Gene-Disease associations (from GenCC):

• hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000772608.1. 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
	PIGM	NM_145167.3	MANE Select	c.-270C>G		upstream_gene	N/A	NP_660150.1	Q9H3S5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ10	ENST00000509700.2	TSL:5	c.669+9825C>G		intron	N/A	ENSP00000491416.1	A0A1W2PPI0
	KCNJ10	ENST00000639408.2	TSL:5	c.587+8493C>G		intron	N/A	ENSP00000491635.1	A0A1W2PQC0
	KCNJ10	ENST00000637644.1	TSL:5	c.487+10037C>G		intron	N/A	ENSP00000490282.1	A0A1B0GUX2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000248 AC: 1 AN: 403074 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 212516

African (AFR) AF: 0.00 AC: 0 AN: 11642

American (AMR) AF: 0.00 AC: 0 AN: 18064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12506

East Asian (EAS) AF: 0.00 AC: 0 AN: 25908

South Asian (SAS) AF: 0.00 AC: 0 AN: 45778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1756

European-Non Finnish (NFE) AF: 0.00000426 AC: 1 AN: 234916

Other (OTH) AF: 0.00 AC: 0 AN: 22940

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: no classifications from unflagged records

Revision: no classifications from unflagged records

Pathogenic	VUS	Benign	Condition
1	-	-	Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.94
PhyloP100		3.9
PromoterAI		-0.47	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587776528; hg19: chr1-160001799;