9-101476056-C-A

Variant names:

• chr9-101476056-C-A
• rs1470427127
• NM_032342.3:c.1037G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032342.3(PGAP4):​c.1037G>T​(p.Arg346Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R346Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PGAP4 NM_032342.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26867262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP4	NM_032342.3	c.1037G>T	p.Arg346Leu	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.1037G>T	p.Arg346Leu	missense_variant	Exon 2 of 2	1	NM_032342.3	ENSP00000363981.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	.;.;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	M;M;M
PhyloP100		5.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.38
Sift	Benign	0.045	D;D;D
Sift4G	Benign	0.18	T;T;T
Polyphen		0.0070	B;B;B
Vest4		0.49
MutPred		0.49		Gain of methylation at R345 (P = 0.0687);Gain of methylation at R345 (P = 0.0687);Gain of methylation at R345 (P = 0.0687);
MVP		0.14
MPC		1.4
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.44
gMVP		0.86
Mutation Taster		=59/41	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: rs1470427127; hg19: chr9-104238338;