rs115580413

Variant summary

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

The ENST00000264167.11(AGPS):ā€‹c.1173C>Gā€‹(p.Gly391=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,605,490 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.014 ( 46 hom., cov: 32)
Exomes š‘“: 0.0015 ( 41 hom. )

Consequence

AGPS
ENST00000264167.11 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.37
Variant links:
Genes affected
AGPS (HGNC:327): (alkylglycerone phosphate synthase) This gene is a member of the FAD-binding oxidoreductase/transferase type 4 family. It encodes a protein that catalyzes the second step of ether lipid biosynthesis in which acyl-dihydroxyacetonephosphate (DHAP) is converted to alkyl-DHAP by the addition of a long chain alcohol and the removal of a long-chain acid anion. The protein is localized to the inner aspect of the peroxisomal membrane and requires FAD as a cofactor. Mutations in this gene have been associated with rhizomelic chondrodysplasia punctata, type 3 and Zellweger syndrome. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 2-177482126-C-G is Benign according to our data. Variant chr2-177482126-C-G is described in ClinVar as [Benign]. Clinvar id is 157710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.37 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2085/151742) while in subpopulation AFR AF= 0.0471 (1953/41446). AF 95% confidence interval is 0.0454. There are 46 homozygotes in gnomad4. There are 977 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 46 Mitochondrial gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGPSNM_003659.4 linkuse as main transcriptc.1173C>G p.Gly391= synonymous_variant 11/20 ENST00000264167.11 NP_003650.1
AGPSXM_011512041.3 linkuse as main transcriptc.903C>G p.Gly301= synonymous_variant 11/20 XP_011510343.1
AGPSXM_047446104.1 linkuse as main transcriptc.903C>G p.Gly301= synonymous_variant 11/20 XP_047302060.1
AGPSXM_047446105.1 linkuse as main transcript downstream_gene_variant XP_047302061.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGPSENST00000264167.11 linkuse as main transcriptc.1173C>G p.Gly391= synonymous_variant 11/201 NM_003659.4 ENSP00000264167 A2

Frequencies

GnomAD3 genomes
AF:
0.0137
AC:
2079
AN:
151622
Hom.:
46
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0471
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00597
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000192
Gnomad OTH
AF:
0.0130
GnomAD3 exomes
AF:
0.00364
AC:
912
AN:
250886
Hom.:
17
AF XY:
0.00271
AC XY:
367
AN XY:
135666
show subpopulations
Gnomad AFR exome
AF:
0.0486
Gnomad AMR exome
AF:
0.00232
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000203
Gnomad OTH exome
AF:
0.00278
GnomAD4 exome
AF:
0.00149
AC:
2167
AN:
1453748
Hom.:
41
Cov.:
30
AF XY:
0.00133
AC XY:
959
AN XY:
723366
show subpopulations
Gnomad4 AFR exome
AF:
0.0491
Gnomad4 AMR exome
AF:
0.00265
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000166
Gnomad4 OTH exome
AF:
0.00299
GnomAD4 genome
AF:
0.0137
AC:
2085
AN:
151742
Hom.:
46
Cov.:
32
AF XY:
0.0132
AC XY:
977
AN XY:
74158
show subpopulations
Gnomad4 AFR
AF:
0.0471
Gnomad4 AMR
AF:
0.00596
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000192
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.00415
Hom.:
5
Bravo
AF:
0.0154
Asia WGS
AF:
0.00232
AC:
8
AN:
3464

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxAug 26, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoAug 28, 2013- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Rhizomelic chondrodysplasia punctata type 3 Benign:3
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesApr 28, 2022- -
Likely benign, no assertion criteria providedclinical testingNatera, Inc.Dec 02, 2019- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
13
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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: rs115580413; hg19: chr2-178346854; API