rs869025323

Variant names:

• chr4-88523797-C-A
• rs869025323
• NM_032906.5:c.-97G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-88523797-C-A
• chr4-88523797-C-T

Variant summary

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

The NM_032906.5(PYURF):​c.-97G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,044,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: PYURF NM_032906.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92
• Publications: 0 publications found

Genes affected

PYURF (HGNC:44317): (PIGY upstream open reading frame) The product of this gene, which is well-conserved, is encoded by the same bicistronic transcript that encodes phosphatidylinositol glycan anchor biosynthesis, class Y, but the two proteins are unrelated. This gene represents the protein encoded by the upstream open reading frame, while the protein encoded by the downstream open reading frame is represented by GeneID:84992. [provided by RefSeq, Aug 2012]

PIGY (HGNC:28213): (phosphatidylinositol glycan anchor biosynthesis class Y) The protein encoded by this gene is part of the GPI-N-acetylglucosaminyltransferase (GIP-GnT) complex which initiates the biosynthesis of glycosylphosphatidylinositol (GPI). GPI is synthesized in the endoplasmic reticulum and serves as an anchor for many surface proteins. Proteins containing GPI anchors can have an important role in cell-cell interactions. The transcript for this gene is bicistronic. The downstream open reading frame encodes this GPI-GnT complex protein, while the upstream open reading frame encodes a protein with unknown function, as represented by GeneID:100996939. [provided by RefSeq, Aug 2012]

HERC3 (HGNC:4876): (HECT and RLD domain containing E3 ubiquitin protein ligase 3) This gene encodes a member the HERC ubiquitin ligase family. The encoded protein is located in the cytosol and binds ubiquitin via a HECT domain. Mutations in this gene have been associated with colorectal and gastric carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

PIGY-DT (HGNC:54080): (PIGY divergent transcript)

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=-0.67).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032906.5. 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
	PYURF	NM_032906.5	MANE Select	c.-97G>T		upstream_gene	N/A	NP_116295.1
	PIGY	NM_001042616.3	MANE Select	c.-540G>T		upstream_gene	N/A	NP_001036081.1
	HERC3	NM_001375482.1		c.-223C>A		upstream_gene	N/A	NP_001362411.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYURF	ENST00000273968.5	TSL:1 MANE Select	c.-97G>T		upstream_gene	N/A	ENSP00000273968.4
	PIGY	ENST00000527353.2	TSL:6 MANE Select	c.-540G>T		upstream_gene	N/A	ENSP00000432688.1
	HERC3	ENST00000512194.2	TSL:5	c.-361C>A		upstream_gene	N/A	ENSP00000421021.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000287 AC: 3 AN: 1044586 Hom.: 0 Cov.: 14 AF XY: 0.00000391 AC XY: 2 AN XY: 511920

African (AFR) AF: 0.00 AC: 0 AN: 19894

American (AMR) AF: 0.00 AC: 0 AN: 12886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16206

East Asian (EAS) AF: 0.0000356 AC: 1 AN: 28088

South Asian (SAS) AF: 0.00 AC: 0 AN: 53212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29684

Middle Eastern (MID) AF: 0.000325 AC: 1 AN: 3080

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 836660

Other (OTH) AF: 0.0000223 AC: 1 AN: 44876

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	20
DANN	Benign	0.95
PhyloP100		2.9
PromoterAI		-0.84	Under-expression

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: rs869025323; hg19: chr4-89444948;