NM_032342.3:c.1028C>A

Variant names:

• chr9-101476065-G-T
• rs746600970
• NM_032342.3:c.1028C>A

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.1028C>A​(p.Ala343Glu) 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 benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A343V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGAP4 NM_032342.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.70
• Publications: 1 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=0.14850241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP4	NM_032342.3	c.1028C>A	p.Ala343Glu	missense_variant	Exon 2 of 2	ENST00000374848.8	NP_115718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP4	ENST00000374848.8	c.1028C>A	p.Ala343Glu	missense_variant	Exon 2 of 2	1	NM_032342.3	ENSP00000363981.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	.;.;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N;N
PhyloP100		7.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.091
Sift	Benign	0.034	D;D;D
Sift4G	Benign	0.15	T;T;T
Polyphen		0.095	B;B;B
Vest4		0.29
MutPred		0.34		Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.085
MPC		0.56
ClinPred		0.68	D
GERP RS		4.8
Varity_R		0.21
gMVP		0.86
Mutation Taster		=75/25	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

dbSNP: rs746600970; hg19: chr9-104238347;