9-101476794-G-A

Variant names:

• chr9-101476794-G-A
• NM_032342.3:c.299C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032342.3(PGAP4):​c.299C>T​(p.Pro100Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGAP4 NM_032342.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.66
• Publications: 0 publications found

Genes affected

PGAP4 (HGNC:28180): (post-GPI attachment to proteins GalNAc transferase 4) Enables glycosyltransferase activity. Involved in GPI anchor biosynthetic process. Located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM246-AS1 (HGNC:51191): (TMEM246 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032342.3. 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
	PGAP4	NM_032342.3	MANE Select	c.299C>T	p.Pro100Leu	missense	Exon 2 of 2	NP_115718.1	Q9BRR3
	PGAP4	NM_001303107.2		c.299C>T	p.Pro100Leu	missense	Exon 3 of 3	NP_001290036.1	Q9BRR3
	PGAP4	NM_001303108.2		c.299C>T	p.Pro100Leu	missense	Exon 2 of 2	NP_001290037.1	Q9BRR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAP4	ENST00000374848.8	TSL:1 MANE Select	c.299C>T	p.Pro100Leu	missense	Exon 2 of 2	ENSP00000363981.3	Q9BRR3
	PGAP4	ENST00000374851.1	TSL:1	c.299C>T	p.Pro100Leu	missense	Exon 4 of 4	ENSP00000363984.1	Q9BRR3
	PGAP4	ENST00000374847.5	TSL:3	c.299C>T	p.Pro100Leu	missense	Exon 3 of 3	ENSP00000363980.1	Q9BRR3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.5	L
PhyloP100		9.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.027	D
Sift4G	Benign	0.072	T
Polyphen		0.89	P
Vest4		0.60
MutPred		0.51		Gain of sheet (P = 0.0221)
MVP		0.18
MPC		1.2
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.17
gMVP		0.75
Mutation Taster		=61/39	polymorphism

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

hg19: chr9-104239076;