NM_004855.5:c.1618T>C

Variant names:

• chr15-55355385-T-C
• rs919526409
• NM_004855.5:c.1618T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004855.5(PIGB):​c.1618T>C​(p.Tyr540His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIGB NM_004855.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

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.1618T>C	p.Tyr540His	missense	Exon 12 of 12	NP_004846.4
	CCPG1	NM_001204450.2	MANE Select	c.*835A>G		3_prime_UTR	Exon 9 of 9	NP_001191379.1	Q9ULG6-5
	CCPG1	NM_004748.6		c.*4114A>G		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.1618T>C	p.Tyr540His	missense	Exon 12 of 12	ENSP00000164305.5	Q92521
	CCPG1	ENST00000442196.8	TSL:2 MANE Select	c.*835A>G		3_prime_UTR	Exon 9 of 9	ENSP00000403400.3	Q9ULG6-5
	CCPG1	ENST00000310958.10	TSL:1	c.*4114A>G		3_prime_UTR	Exon 8 of 8	ENSP00000311656.6	Q9ULG6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.45
Sift	Benign	0.042	D
Sift4G	Uncertain	0.044	D
Polyphen		0.94	P
Vest4		0.86
MutPred		0.70		Gain of disorder (P = 0.0321)
MVP		0.71
MPC		0.19
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.35
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs919526409; hg19: chr15-55647583;