rs2941503

chr17-39672492-A-Gchr17-39672492-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033419.5(PGAP3):c.*311T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 431,570 control chromosomes in the GnomAD database, including 97,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31436 hom., cov: 32)
  • Exomes 𝑓: 0.68 (65954 hom.)
• Consequence: PGAP3 NM_033419.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.128

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003986627).
• BP6: Variant 17-39672492-A-G is Benign according to our data. Variant chr17-39672492-A-G is described in ClinVar as [Benign]. Clinvar id is 1232753.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
PGAP3	NM_033419.5	c.*311T>C		3_prime_UTR_variant	8/8	ENST00000300658.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP3	ENST00000300658.9	c.*311T>C		3_prime_UTR_variant	8/8	1	NM_033419.5	P1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96831 AN: 151924 Hom.: 31411 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.681 AC: 190224 AN: 279528 Hom.: 65954 Cov.: 0 AF XY: 0.688 AC XY: 101785 AN XY: 147992

Gnomad4 AFR exome AF: 0.539

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.700

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.707

Gnomad4 NFE exome AF: 0.697

Gnomad4 OTH exome AF: 0.668

GnomAD4 genome AF: 0.637 AC: 96915 AN: 152042 Hom.: 31436 Cov.: 32 AF XY: 0.636 AC XY: 47279 AN XY: 74314

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.634

Alfa AF: 0.690 Hom.: 47944

Bravo AF: 0.619

TwinsUK AF: 0.691 AC: 2562

ALSPAC AF: 0.690 AC: 2661

Asia WGS AF: 0.616 AC: 2145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.7
Dann	Benign	0.58
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0040	T
MutationTaster	Benign	1.0	P;P;P
Sift4G	Benign	0.72	T
Vest4		0.090
MVP		0.59
GERP RS		-7.4

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: rs2941503; hg19: chr17-37828745;