16-374420-C-G

Position:

• chr16-374420-C-G

Variant summary

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

The NM_021259.3(PGAP6):​c.1577-21G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,543,268 control chromosomes in the GnomAD database, including 260,227 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25301 hom., cov: 33)
  • Exomes 𝑓: 0.58 (234926 hom.)
• Consequence: PGAP6 NM_021259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536

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]

PGAP6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP6	NM_021259.3	c.1577-21G>C		intron_variant		ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1	c.998-21G>C		intron_variant			XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAP6	ENST00000431232.7	c.1577-21G>C		intron_variant		1	NM_021259.3	ENSP00000401338.2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86789 AN: 151808 Hom.: 25269 Cov.: 33

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.522

GnomAD3 exomes AF: 0.542 AC: 106738 AN: 196782 Hom.: 29952 AF XY: 0.555 AC XY: 59451 AN XY: 107182

Gnomad AFR exome AF: 0.622

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.448

Gnomad EAS exome AF: 0.316

Gnomad SAS exome AF: 0.715

Gnomad FIN exome AF: 0.559

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.577 AC: 803286 AN: 1391342 Hom.: 234926 Cov.: 40 AF XY: 0.581 AC XY: 398633 AN XY: 686146

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.708

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.585

Gnomad4 OTH exome AF: 0.561

GnomAD4 genome AF: 0.572 AC: 86882 AN: 151926 Hom.: 25301 Cov.: 33 AF XY: 0.571 AC XY: 42376 AN XY: 74228

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.523

Alfa AF: 0.472 Hom.: 2331

Bravo AF: 0.559

Asia WGS AF: 0.544 AC: 1890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.44
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs3743888; hg19: chr16-424420; COSMIC: COSV51741206; COSMIC: COSV51741206;