15-55355337-TTC-CTA

Variant names:

• chr15-55355337-TTC-CTA
• NM_004855.5:c.1570_1572delTTCinsCTA
• PIGB p.Phe524Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004855.5(PIGB):​c.1570_1572delTTCinsCTA​(p.Phe524Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F524F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIGB NM_004855.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.58
• Publications: 0 publications found

Genes affected

PIGB (HGNC:8959): (phosphatidylinositol glycan anchor biosynthesis class B) 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 found on many blood cells and serves to anchor proteins to the cell surface. This gene is thought to encode a member of a family of dolichol-phosphate-mannose (Dol-P-Man) dependent mannosyltransferases. [provided by RefSeq, Jul 2008]

CCPG1 (HGNC:24227): (cell cycle progression 1) Involved in positive regulation of cell cycle and positive regulation of cell population proliferation. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004855.5. 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
	PIGB	NM_004855.5	MANE Select	c.1570_1572delTTCinsCTA	p.Phe524Leu	missense	N/A	NP_004846.4
	CCPG1	NM_001204450.2	MANE Select	c.*881_*883delGAAinsTAG		3_prime_UTR	Exon 9 of 9	NP_001191379.1	Q9ULG6-5
	CCPG1	NM_004748.6		c.*4160_*4162delGAAinsTAG		3_prime_UTR	Exon 8 of 8	NP_004739.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGB	ENST00000164305.10	TSL:1 MANE Select	c.1570_1572delTTCinsCTA	p.Phe524Leu	missense	N/A	ENSP00000164305.5	Q92521
	CCPG1	ENST00000442196.8	TSL:2 MANE Select	c.*881_*883delGAAinsTAG		3_prime_UTR	Exon 9 of 9	ENSP00000403400.3	Q9ULG6-5
	CCPG1	ENST00000310958.10	TSL:1	c.*4160_*4162delGAAinsTAG		3_prime_UTR	Exon 8 of 8	ENSP00000311656.6	Q9ULG6-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-55647535;