chr17-78390193-C-A

Variant names:

• chr17-78390193-C-A
• rs2090205
• NM_024419.5:c.144-2283C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024419.5(PGS1):​c.144-2283C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,900 control chromosomes in the GnomAD database, including 3,290 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 0.20 (3290 hom., cov: 30)
• Consequence: PGS1 NM_024419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 12 publications found

Genes affected

PGS1 (HGNC:30029): (phosphatidylglycerophosphate synthase 1) Predicted to enable CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity and calcium ion binding activity. Predicted to be involved in cardiolipin biosynthetic process and diacylglycerol metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGS1	NM_024419.5	c.144-2283C>A		intron_variant	Intron 1 of 9	ENST00000262764.11	NP_077733.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGS1	ENST00000262764.11	c.144-2283C>A		intron_variant	Intron 1 of 9	1	NM_024419.5	ENSP00000262764.5

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30811 AN: 151782 Hom.: 3285 Cov.: 30

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.203 AC: 30835 AN: 151900 Hom.: 3290 Cov.: 30 AF XY: 0.204 AC XY: 15113 AN XY: 74232

African (AFR) AF: 0.162 AC: 6719 AN: 41458

American (AMR) AF: 0.155 AC: 2360 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 789 AN: 3466

East Asian (EAS) AF: 0.246 AC: 1265 AN: 5136

South Asian (SAS) AF: 0.249 AC: 1197 AN: 4812

European-Finnish (FIN) AF: 0.194 AC: 2044 AN: 10518

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15894 AN: 67952

Other (OTH) AF: 0.184 AC: 388 AN: 2106

Alfa AF: 0.192 Hom.: 461

Bravo AF: 0.197

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.66
DANN	Benign	0.73
PhyloP100		-2.1
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: rs2090205; hg19: chr17-76386274;