NM_032342.3:c.759C>G

Variant names:

• chr9-101476334-G-C
• NM_032342.3:c.759C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032342.3(PGAP4):​c.759C>G​(p.His253Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: 1.71
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11589283).

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.759C>G	p.His253Gln	missense	Exon 2 of 2	NP_115718.1	Q9BRR3
	PGAP4	NM_001303107.2		c.759C>G	p.His253Gln	missense	Exon 3 of 3	NP_001290036.1	Q9BRR3
	PGAP4	NM_001303108.2		c.759C>G	p.His253Gln	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.759C>G	p.His253Gln	missense	Exon 2 of 2	ENSP00000363981.3	Q9BRR3
	PGAP4	ENST00000374851.1	TSL:1	c.759C>G	p.His253Gln	missense	Exon 4 of 4	ENSP00000363984.1	Q9BRR3
	PGAP4	ENST00000374847.5	TSL:3	c.759C>G	p.His253Gln	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	Benign	0.30
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.039
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.13
Sift	Benign	0.43	T
Sift4G	Benign	0.46	T
Polyphen		0.058	B
Vest4		0.16
MutPred		0.22		Gain of helix (P = 0.0225)
MVP		0.10
MPC		0.42
ClinPred		0.12	T
GERP RS		4.8
Varity_R		0.074
gMVP		0.71
Mutation Taster		=86/14	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: chr9-104238616;