chr2-177421978-G-C

Position:

• chr2-177421978-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003659.4(AGPS):​c.350+1620G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 152,064 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.035 (205 hom., cov: 32)
• Consequence: AGPS NM_003659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGPS	NM_003659.4	c.350+1620G>C		intron_variant		ENST00000264167.11
AGPS	XM_011512041.3	c.80+1620G>C		intron_variant
AGPS	XM_047446104.1	c.80+1620G>C		intron_variant
AGPS	XM_047446105.1	c.350+1620G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGPS	ENST00000264167.11	c.350+1620G>C		intron_variant		1	NM_003659.4	A2

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5303 AN: 151946 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.0292

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00876

Gnomad OTH AF: 0.0296

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0350 AC: 5321 AN: 152064 Hom.: 205 Cov.: 32 AF XY: 0.0345 AC XY: 2566 AN XY: 74362

Gnomad4 AFR AF: 0.0967

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.0292

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0553

Gnomad4 FIN AF: 0.00631

Gnomad4 NFE AF: 0.00876

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.00254 Hom.: 0

Bravo AF: 0.0372

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs10497507; hg19: chr2-178286706;