8-6728358-G-C

Position:

• chr8-6728358-G-C

Variant summary

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

The NM_018361.5(AGPAT5):​c.290-2353G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,278 control chromosomes in the GnomAD database, including 45,134 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 0.76 (45134 hom., cov: 34)
• Consequence: AGPAT5 NM_018361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

Genes affected

AGPAT5 (HGNC:20886): (1-acylglycerol-3-phosphate O-acyltransferase 5) This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. This integral membrane protein converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. A pseudogene of this gene is present on the Y chromosome. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGPAT5	NM_018361.5	c.290-2353G>C		intron_variant		ENST00000285518.11
AGPAT5	XM_047421938.1	c.-164-2353G>C		intron_variant
AGPAT5	XM_047421939.1	c.-164-2353G>C		intron_variant
AGPAT5	XM_047421940.1	c.290-2353G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGPAT5	ENST00000285518.11	c.290-2353G>C		intron_variant		1	NM_018361.5	P1
AGPAT5	ENST00000518327.1	c.195+19471G>C		intron_variant		1
AGPAT5	ENST00000523234.5	c.220-2353G>C		intron_variant, NMD_transcript_variant		5
AGPAT5	ENST00000523586.1	c.*222-2353G>C		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115508 AN: 152160 Hom.: 45075 Cov.: 34

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.759 AC: 115626 AN: 152278 Hom.: 45134 Cov.: 34 AF XY: 0.759 AC XY: 56531 AN XY: 74452

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.756

Alfa AF: 0.591 Hom.: 1606

Bravo AF: 0.784

Asia WGS AF: 0.706 AC: 2454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.7
DANN	Benign	0.68

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: rs2980683; hg19: chr8-6585879;