rs2071915

chr16-376432-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021259.3(PGAP6):c.928A>G(p.Ile310Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,581,270 control chromosomes in the GnomAD database, including 260,426 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.57 (25112 hom., cov: 34)
  • Exomes 𝑓: 0.57 (235314 hom.)
• Consequence: PGAP6 NM_021259.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

Genes affected

PGAP6 (HGNC:17205): (post-GPI attachment to proteins 6) Predicted to enable phospholipase A2 activity. Located in extracellular exosome and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7885794E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP6	NM_021259.3	c.928A>G	p.Ile310Val	missense_variant	6/13	ENST00000431232.7
PGAP6	XM_047434413.1	c.349A>G	p.Ile117Val	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP6	ENST00000431232.7	c.928A>G	p.Ile310Val	missense_variant	6/13	1	NM_021259.3	P2
PGAP6	ENST00000250930.7	c.349A>G	p.Ile117Val	missense_variant	6/13	2		A2
PGAP6	ENST00000475348.1	n.44A>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86541 AN: 152056 Hom.: 25083 Cov.: 34

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.520

GnomAD3 exomes AF: 0.535 AC: 119652 AN: 223568 Hom.: 33347 AF XY: 0.548 AC XY: 66125 AN XY: 120662

Gnomad AFR exome AF: 0.628

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.315

Gnomad SAS exome AF: 0.698

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.561

Gnomad OTH exome AF: 0.538

GnomAD4 exome AF: 0.570 AC: 814393 AN: 1429094 Hom.: 235314 Cov.: 71 AF XY: 0.573 AC XY: 405210 AN XY: 706706

Gnomad4 AFR exome AF: 0.641

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.569 AC: 86633 AN: 152176 Hom.: 25112 Cov.: 34 AF XY: 0.569 AC XY: 42312 AN XY: 74392

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.522

Alfa AF: 0.549 Hom.: 37603

Bravo AF: 0.557

TwinsUK AF: 0.591 AC: 2190

ALSPAC AF: 0.580 AC: 2234

ESP6500AA AF: 0.624 AC: 2746

ESP6500EA AF: 0.567 AC: 4870

ExAC AF: 0.539 AC: 65058

Asia WGS AF: 0.541 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.0050
Dann	Benign	0.073
DEOGEN2	Benign	0.0037	T;.
Eigen	Benign	-2.8
Eigen_PC	Benign	-2.9
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.19	T;T
MetaRNN	Benign	0.0000018	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.10	N;N
REVEL	Benign	0.0040
Sift	Benign	0.31	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.0	B;.
Vest4		0.029
MPC		0.037
ClinPred		0.032	T
GERP RS		-9.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.014
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2071915; hg19: chr16-426432; COSMIC: COSV51737855; COSMIC: COSV51737855;