Variant chr2-177392823-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003659.4(AGPS):c.34G>C(p.Gly12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

AGPS
NM_003659.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0120

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]

AGPS links:

AGPS (HGNC:):

AGPS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05728057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPS	NM_003659.4 linkuse as main transcript	c.34G>C	p.Gly12Arg	missense_variant	1/20	ENST00000264167.11	NP_003650.1	O00116
AGPS	XM_047446105.1 linkuse as main transcript	c.34G>C	p.Gly12Arg	missense_variant	1/10		XP_047302061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPS	ENST00000264167.11 linkuse as main transcript	c.34G>C	p.Gly12Arg	missense_variant	1/20	1	NM_003659.4	ENSP00000264167.4		O00116

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1398870

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691878

show subpopulations

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:

0.00000368

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 31, 2021

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AGPS-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces glycine with arginine at codon 12 of the AGPS protein (p.Gly12Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Benign

5.1

DANN

Benign

0.82

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.48

T;T

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.057

T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.32

N;N

REVEL

Uncertain

0.39

Sift

Benign

0.64

T;D

Sift4G

Benign

0.64

T;D

Polyphen

0.0

B;.

Vest4

0.27

MutPred

0.23

Gain of methylation at G12 (P = 0.0038);Gain of methylation at G12 (P = 0.0038);

MVP

0.49

MPC

1.0

ClinPred

0.057

GERP RS

-0.80

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.031

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over