17-39672243-T-C

Position:

• chr17-39672243-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033419.5(PGAP3):​c.*560A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 155,638 control chromosomes in the GnomAD database, including 32,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31519 hom., cov: 32)
  • Exomes 𝑓: 0.64 (760 hom.)
• Consequence: PGAP3 NM_033419.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.59

Genes affected

PGAP3 (HGNC:23719): (post-GPI attachment to proteins phospholipase 3) This gene encodes a glycosylphosphatidylinositol (GPI)-specific phospholipase that primarily localizes to the Golgi apparatus. This ubiquitously expressed gene is predicted to encode a seven-transmembrane protein that removes unsaturated fatty acids from the sn-2 position of GPI. The remodeling of the constituent fatty acids on GPI is thought to be important for the proper association between GPI-anchored proteins and lipid rafts. The tethering of proteins to plasma membranes via posttranslational GPI-anchoring is thought to play a role in protein sorting and trafficking. Mutations in this gene cause an autosomal recessive form of neurologic hyperphosphatasia with cognitive disability (HPMRS4). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

PGAP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038244426).
• BP6: Variant 17-39672243-T-C is Benign according to our data. Variant chr17-39672243-T-C is described in ClinVar as [Benign]. Clinvar id is 1278119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP3	NM_033419.5	c.*560A>G		3_prime_UTR_variant	8/8	ENST00000300658.9	NP_219487.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAP3	ENST00000300658	c.*560A>G		3_prime_UTR_variant	8/8	1	NM_033419.5	ENSP00000300658.4

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96990 AN: 151970 Hom.: 31490 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.636 AC: 2257 AN: 3550 Hom.: 760 Cov.: 0 AF XY: 0.648 AC XY: 1221 AN XY: 1884

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.708

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.755

Gnomad4 FIN exome AF: 0.596

Gnomad4 NFE exome AF: 0.671

Gnomad4 OTH exome AF: 0.577

GnomAD4 genome AF: 0.638 AC: 97078 AN: 152088 Hom.: 31519 Cov.: 32 AF XY: 0.637 AC XY: 47365 AN XY: 74348

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.634

Alfa AF: 0.650 Hom.: 8195

Bravo AF: 0.620

TwinsUK AF: 0.692 AC: 2567

ALSPAC AF: 0.691 AC: 2665

Asia WGS AF: 0.617 AC: 2149 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.61
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0038	T
MutationTaster	Benign	1.0	P;P;P
Sift4G	Benign	1.0	T
Vest4		0.15
MVP		0.63
GERP RS		-5.2

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: rs2952151; hg19: chr17-37828496;