ENST00000300730.10:c.145T>G

Variant names:

• chr11-3808299-T-G
• rs183093939
• ENST00000300730.10:c.145T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The ENST00000300730.10(PGAP2):​c.145T>G​(p.Trp49Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W49R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGAP2 ENST00000300730.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

Genes affected

PGAP2 (HGNC:17893): (post-GPI attachment to proteins 2) The protein encoded by this gene plays a role in the maturation of glycosylphosphatidylinositol (GPI) anchors on GPI-anchored proteins. Mutations in this gene are associated with an autosomal recessive syndrome characterized by hyperphosphatasia and intellectual disability. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a chain Post-GPI attachment to proteins factor 2 (size 253) in uniprot entity PGAP2_HUMAN there are 29 pathogenic changes around while only 9 benign (76%) in ENST00000300730.10
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3398873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP2	NM_001256236.1	c.145T>G	p.Trp49Gly	missense_variant	Exon 2 of 8		NP_001243165.1
PGAP2	NM_001283038.1	c.145T>G	p.Trp49Gly	missense_variant	Exon 2 of 7		NP_001269967.1
PGAP2	NM_001145438.2	c.145T>G	p.Trp49Gly	missense_variant	Exon 2 of 7		NP_001138910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP2	ENST00000300730.10	c.145T>G	p.Trp49Gly	missense_variant	Exon 2 of 7	1		ENSP00000300730.6
PGAP2	ENST00000396993	c.-320T>G		5_prime_UTR_variant	Exon 2 of 6	1		ENSP00000380190.6
PGAP2	ENST00000465237.6	n.81T>G		non_coding_transcript_exon_variant	Exon 2 of 3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.0018	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Benign	0.97
Eigen	Benign	0.17
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.18	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.13	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D;D
Polyphen		0.97	D;.
Vest4		0.52
MutPred		0.48		Gain of disorder (P = 0.0063);Gain of disorder (P = 0.0063);
MVP		0.45
ClinPred		0.70	D
GERP RS		3.1

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: rs183093939; hg19: chr11-3829529;