rs587783176

Variant names:

• chr2-177420264-A-C
• rs73029113
• NM_003659.4:c.261-5A>C

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.261-5A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,586,830 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (67 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (73 hom.)
• Consequence: AGPS NM_003659.4 splice_region, intron
• Scores: Splicing: ADA: 0.00009745
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.931
• Publications: 1 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=-0.76).
• BP6: Variant 2-177420264-A-C is Benign according to our data. Variant chr2-177420264-A-C is described in ClinVar as Benign. ClinVar VariationId is 157713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003659.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPS	NM_003659.4	MANE Select	c.261-5A>C		splice_region intron	N/A	NP_003650.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPS	ENST00000264167.11	TSL:1 MANE Select	c.261-5A>C		splice_region intron	N/A	ENSP00000264167.4
	AGPS	ENST00000642466.2		c.261-5A>C		splice_region intron	N/A	ENSP00000494433.2
	AGPS	ENST00000679459.1		c.261-5A>C		splice_region intron	N/A	ENSP00000506137.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2547 AN: 151746 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00971

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000414

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00447 AC: 1119 AN: 250340 AF XY: 0.00326

Gnomad AFR exome AF: 0.0564

Gnomad AMR exome AF: 0.00374

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000424

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00188 AC: 2702 AN: 1434966 Hom.: 73 Cov.: 27 AF XY: 0.00167 AC XY: 1197 AN XY: 715588

African (AFR) AF: 0.0603 AC: 1973 AN: 32710

American (AMR) AF: 0.00412 AC: 184 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25886

East Asian (EAS) AF: 0.00 AC: 0 AN: 39368

South Asian (SAS) AF: 0.000222 AC: 19 AN: 85622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52966

Middle Eastern (MID) AF: 0.00681 AC: 39 AN: 5724

European-Non Finnish (NFE) AF: 0.000186 AC: 202 AN: 1088524

Other (OTH) AF: 0.00474 AC: 282 AN: 59500

GnomAD4 genome AF: 0.0169 AC: 2562 AN: 151864 Hom.: 67 Cov.: 32 AF XY: 0.0166 AC XY: 1234 AN XY: 74220

African (AFR) AF: 0.0566 AC: 2349 AN: 41520

American (AMR) AF: 0.00970 AC: 148 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.000414 AC: 28 AN: 67702

Other (OTH) AF: 0.0138 AC: 29 AN: 2106

Alfa AF: 0.00716 Hom.: 11

Bravo AF: 0.0189

Asia WGS AF: 0.00492 AC: 18 AN: 3470

EpiCase AF: 0.000437

EpiControl AF: 0.000474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Rhizomelic chondrodysplasia punctata type 3 (2)
-	-	1	not specified (1)
-	-	1	Rhizomelic chondrodysplasia punctata (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.3
DANN	Benign	0.63
PhyloP100		0.93
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000097
dbscSNV1_RF	Benign	0.0040
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: rs73029113; hg19: chr2-178284992;