rs3213945

Variant names:

• chr2-177538058-G-T
• rs3213945
• NM_003659.4:c.1856-16G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003659.4(AGPS):​c.1856-16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,246 control chromosomes in the GnomAD database, including 10,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (920 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9862 hom.)
• Consequence: AGPS NM_003659.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0780
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• alkylglycerone-phosphate synthase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• rhizomelic chondrodysplasia punctata type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-177538058-G-T is Benign according to our data. Variant chr2-177538058-G-T is described in ClinVar as Benign. ClinVar VariationId is 259117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGPS	NM_003659.4	c.1856-16G>T		intron_variant	Intron 19 of 19	ENST00000264167.11	NP_003650.1
AGPS	XM_011512041.3	c.1586-16G>T		intron_variant	Intron 19 of 19		XP_011510343.1
AGPS	XM_047446104.1	c.1586-16G>T		intron_variant	Intron 19 of 19		XP_047302060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGPS	ENST00000264167.11	c.1856-16G>T		intron_variant	Intron 19 of 19	1	NM_003659.4	ENSP00000264167.4

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13926 AN: 151972 Hom.: 917 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.0976

GnomAD2 exomes AF: 0.114 AC: 28563 AN: 251092 AF XY: 0.117

Gnomad AFR exome AF: 0.0528

Gnomad AMR exome AF: 0.0664

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.349

Gnomad FIN exome AF: 0.0768

Gnomad NFE exome AF: 0.0922

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.103 AC: 149805 AN: 1460156 Hom.: 9862 Cov.: 32 AF XY: 0.104 AC XY: 75859 AN XY: 726430

African (AFR) AF: 0.0591 AC: 1973 AN: 33402

American (AMR) AF: 0.0690 AC: 3081 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3363 AN: 26070

East Asian (EAS) AF: 0.373 AC: 14786 AN: 39658

South Asian (SAS) AF: 0.158 AC: 13617 AN: 86206

European-Finnish (FIN) AF: 0.0795 AC: 4245 AN: 53400

Middle Eastern (MID) AF: 0.143 AC: 821 AN: 5758

European-Non Finnish (NFE) AF: 0.0909 AC: 100971 AN: 1110722

Other (OTH) AF: 0.115 AC: 6948 AN: 60290

GnomAD4 genome AF: 0.0915 AC: 13921 AN: 152090 Hom.: 920 Cov.: 32 AF XY: 0.0930 AC XY: 6915 AN XY: 74372

African (AFR) AF: 0.0564 AC: 2342 AN: 41528

American (AMR) AF: 0.0725 AC: 1106 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1839 AN: 5158

South Asian (SAS) AF: 0.161 AC: 776 AN: 4818

European-Finnish (FIN) AF: 0.0671 AC: 711 AN: 10602

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0931 AC: 6327 AN: 67934

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

Alfa AF: 0.0920 Hom.: 1192

Bravo AF: 0.0909

Asia WGS AF: 0.231 AC: 800 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Dec 15, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 05, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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. -

Rhizomelic chondrodysplasia punctata type 3 Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.5
DANN	Benign	0.74
PhyloP100		0.078
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3213945; hg19: chr2-178402786; COSMIC: COSV51562123;