rs199809707

Variant names:

• chr2-196873710-T-A
• NM_024989.4:c.1475A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-196873710-T-A
• chr2-196873710-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024989.4(PGAP1):​c.1475A>T​(p.Asn492Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,820 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PGAP1 NM_024989.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

Genes affected

PGAP1 (HGNC:25712): (post-GPI attachment to proteins inositol deacylase 1) The protein encoded by this gene functions early in the glycosylphosphatidylinositol (GPI) biosynthetic pathway, catalyzing the inositol deacylation of GPI. The encoded protein is required for the production of GPI that can attach to proteins, and this may be an important factor in the transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi. Defects in this gene are a cause an autosomal recessive form of cognitive impairment. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP1	NM_024989.4	c.1475A>T	p.Asn492Ile	missense_variant	Exon 15 of 27	ENST00000354764.9	NP_079265.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP1	ENST00000354764.9	c.1475A>T	p.Asn492Ile	missense_variant	Exon 15 of 27	1	NM_024989.4	ENSP00000346809.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459820 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726394

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	0.00056	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;.
Eigen	Benign	-0.075
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0096	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.14
Sift	Benign	0.045	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.81	P;B
Vest4		0.73
MutPred		0.54		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.73
MPC		0.27
ClinPred		0.45	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-197738434;