chr8-6728358-G-C

Variant names:

• chr8-6728358-G-C
• rs2980683
• NM_018361.5:c.290-2353G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

AGPAT5 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AGPAT5	NM_018361.5	c.290-2353G>C		intron_variant	Intron 2 of 7	ENST00000285518.11	NP_060831.2
AGPAT5	XM_047421938.1	c.-164-2353G>C		intron_variant	Intron 1 of 6		XP_047277894.1
AGPAT5	XM_047421939.1	c.-164-2353G>C		intron_variant	Intron 3 of 8		XP_047277895.1
AGPAT5	XM_047421940.1	c.290-2353G>C		intron_variant	Intron 2 of 4		XP_047277896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGPAT5	ENST00000285518.11	c.290-2353G>C		intron_variant	Intron 2 of 7	1	NM_018361.5	ENSP00000285518.6
AGPAT5	ENST00000518327.1	c.193+19471G>C		intron_variant	Intron 1 of 2	1		ENSP00000430751.1
AGPAT5	ENST00000523234.5	n.220-2353G>C		intron_variant	Intron 1 of 6	5		ENSP00000430016.1
AGPAT5	ENST00000523586.1	n.*222-2353G>C		intron_variant	Intron 3 of 3	4		ENSP00000428152.1

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

African (AFR) AF: 0.937 AC: 38947 AN: 41578

American (AMR) AF: 0.810 AC: 12393 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3472

East Asian (EAS) AF: 0.801 AC: 4155 AN: 5190

South Asian (SAS) AF: 0.633 AC: 3058 AN: 4828

European-Finnish (FIN) AF: 0.663 AC: 7020 AN: 10582

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45199 AN: 68012

Other (OTH) AF: 0.756 AC: 1599 AN: 2114

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
PhyloP100		-0.59
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: rs2980683; hg19: chr8-6585879;