rs2941503

Variant names:

• chr17-39672492-A-G
• rs2941503
• NM_033419.5:c.*311T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-39672492-A-G
• chr17-39672492-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.128
• Publications: 39 publications found

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 Gene-Disease associations (from GenCC):

• hyperphosphatasia with intellectual disability syndrome 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• hyperphosphatasia-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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_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 rank	MANE	Protein	UniProt
PGAP3	NM_033419.5	c.*311T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000300658.9	NP_219487.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP3	ENST00000300658.9	c.*311T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_033419.5	ENSP00000300658.4

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

African (AFR) AF: 0.539 AC: 4536 AN: 8416

American (AMR) AF: 0.590 AC: 6526 AN: 11064

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 5953 AN: 8506

East Asian (EAS) AF: 0.448 AC: 7852 AN: 17520

South Asian (SAS) AF: 0.769 AC: 25913 AN: 33712

European-Finnish (FIN) AF: 0.707 AC: 11035 AN: 15598

Middle Eastern (MID) AF: 0.772 AC: 947 AN: 1226

European-Non Finnish (NFE) AF: 0.697 AC: 116680 AN: 167346

Other (OTH) AF: 0.668 AC: 10782 AN: 16140

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

African (AFR) AF: 0.552 AC: 22883 AN: 41444

American (AMR) AF: 0.587 AC: 8974 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2420 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2115 AN: 5156

South Asian (SAS) AF: 0.737 AC: 3555 AN: 4824

European-Finnish (FIN) AF: 0.720 AC: 7631 AN: 10598

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47060 AN: 67956

Other (OTH) AF: 0.634 AC: 1336 AN: 2108

Alfa AF: 0.684 Hom.: 70512

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
PhyloP100		-0.13
Sift4G	Benign	0.72	T
Vest4		0.090
MVP		0.59
GERP RS		-7.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2941503; hg19: chr17-37828745;