rs2090205

Positions:

• chr17-78390193-C-A
• chr17-78390193-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PGS1	NM_024419.5	c.144-2283C>A		intron_variant		ENST00000262764.11	NP_077733.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGS1	ENST00000262764.11	c.144-2283C>A		intron_variant		1	NM_024419.5	ENSP00000262764	P1

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

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.184

Alfa AF: 0.193 Hom.: 450

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

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: rs2090205; hg19: chr17-76386274;