rs149815494

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_024989.4(PGAP1):​c.2007C>T​(p.Ala669Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,612,652 control chromosomes in the GnomAD database, including 320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 37 hom., cov: 32)
Exomes 𝑓: 0.013 ( 283 hom. )

Consequence

PGAP1
NM_024989.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.11
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 2-196847146-G-A is Benign according to our data. Variant chr2-196847146-G-A is described in ClinVar as [Benign]. Clinvar id is 474991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.11 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0129 (1964/152008) while in subpopulation NFE AF= 0.0128 (869/67966). AF 95% confidence interval is 0.0121. There are 37 homozygotes in gnomad4. There are 1163 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PGAP1NM_024989.4 linkuse as main transcriptc.2007C>T p.Ala669Ala synonymous_variant 22/27 ENST00000354764.9 NP_079265.2 Q75T13-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PGAP1ENST00000354764.9 linkuse as main transcriptc.2007C>T p.Ala669Ala synonymous_variant 22/271 NM_024989.4 ENSP00000346809.3 Q75T13-1
PGAP1ENST00000423035.5 linkuse as main transcriptn.*1938C>T non_coding_transcript_exon_variant 23/281 ENSP00000415405.1 F8WD75
PGAP1ENST00000423035.5 linkuse as main transcriptn.*1938C>T 3_prime_UTR_variant 23/281 ENSP00000415405.1 F8WD75
PGAP1ENST00000470179.5 linkuse as main transcriptn.2217C>T non_coding_transcript_exon_variant 17/222

Frequencies

GnomAD3 genomes
AF:
0.0129
AC:
1964
AN:
151890
Hom.:
37
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00193
Gnomad AMI
AF:
0.0285
Gnomad AMR
AF:
0.00407
Gnomad ASJ
AF:
0.00518
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.0843
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0128
Gnomad OTH
AF:
0.0101
GnomAD3 exomes
AF:
0.0136
AC:
3392
AN:
249556
Hom.:
97
AF XY:
0.0134
AC XY:
1817
AN XY:
135146
show subpopulations
Gnomad AFR exome
AF:
0.00174
Gnomad AMR exome
AF:
0.00368
Gnomad ASJ exome
AF:
0.00451
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0811
Gnomad NFE exome
AF:
0.0121
Gnomad OTH exome
AF:
0.0125
GnomAD4 exome
AF:
0.0134
AC:
19565
AN:
1460644
Hom.:
283
Cov.:
30
AF XY:
0.0129
AC XY:
9347
AN XY:
726646
show subpopulations
Gnomad4 AFR exome
AF:
0.00161
Gnomad4 AMR exome
AF:
0.00391
Gnomad4 ASJ exome
AF:
0.00459
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0757
Gnomad4 NFE exome
AF:
0.0131
Gnomad4 OTH exome
AF:
0.00981
GnomAD4 genome
AF:
0.0129
AC:
1964
AN:
152008
Hom.:
37
Cov.:
32
AF XY:
0.0157
AC XY:
1163
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00193
Gnomad4 AMR
AF:
0.00406
Gnomad4 ASJ
AF:
0.00518
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000416
Gnomad4 FIN
AF:
0.0843
Gnomad4 NFE
AF:
0.0128
Gnomad4 OTH
AF:
0.00997
Alfa
AF:
0.00965
Hom.:
4
Bravo
AF:
0.00661
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxFeb 13, 2020- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2024PGAP1: BP4, BP7, BS1, BS2 -
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenAug 30, 2021- -
Intellectual disability, autosomal recessive 42 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
11
DANN
Benign
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149815494; hg19: chr2-197711870; API