17-39672534-G-A

Position:

• chr17-39672534-G-A

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.*269C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 544,726 control chromosomes in the GnomAD database, including 127,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33742 hom., cov: 32)
  • Exomes 𝑓: 0.69 (93948 hom.)
• Consequence: PGAP3 NM_033419.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.13

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=0.0045864284).
• BP6: Variant 17-39672534-G-A is Benign according to our data. Variant chr17-39672534-G-A is described in ClinVar as [Benign]. Clinvar id is 1239136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP3	NM_033419.5	c.*269C>T		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.*269C>T		3_prime_UTR_variant	8/8	1	NM_033419.5	ENSP00000300658.4

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100655 AN: 151918 Hom.: 33700 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.654

GnomAD4 exome AF: 0.686 AC: 269517 AN: 392688 Hom.: 93948 Cov.: 2 AF XY: 0.691 AC XY: 142938 AN XY: 206742

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.708

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.767

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.701

Gnomad4 OTH exome AF: 0.684

GnomAD4 genome AF: 0.663 AC: 100762 AN: 152038 Hom.: 33742 Cov.: 32 AF XY: 0.662 AC XY: 49165 AN XY: 74300

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.656

Alfa AF: 0.685 Hom.: 31542

Bravo AF: 0.649

TwinsUK AF: 0.691 AC: 2563

ALSPAC AF: 0.691 AC: 2663

Asia WGS AF: 0.640 AC: 2226 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.55
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0046	T
MutationTaster	Benign	1.0	P;P;P
Sift4G	Benign	1.0	T
Vest4		0.11
MVP		0.63
GERP RS		-0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs907087; hg19: chr17-37828787;