rs938350

Variant names:

• chr17-78403471-G-A
• rs938350
• NM_024419.5:c.881-97G>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.881-97G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,263,102 control chromosomes in the GnomAD database, including 233,608 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 0.61 (28348 hom., cov: 31)
  • Exomes 𝑓: 0.61 (205260 hom.)
• Consequence: PGS1 NM_024419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.58
• Publications: 14 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGS1	NM_024419.5	c.881-97G>A		intron_variant	Intron 6 of 9	ENST00000262764.11	NP_077733.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGS1	ENST00000262764.11	c.881-97G>A		intron_variant	Intron 6 of 9	1	NM_024419.5	ENSP00000262764.5

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92631 AN: 151854 Hom.: 28331 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.606 AC: 673213 AN: 1111130 Hom.: 205260 AF XY: 0.604 AC XY: 336092 AN XY: 556288

African (AFR) AF: 0.604 AC: 15565 AN: 25766

American (AMR) AF: 0.665 AC: 23548 AN: 35418

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 11665 AN: 19464

East Asian (EAS) AF: 0.441 AC: 16605 AN: 37670

South Asian (SAS) AF: 0.570 AC: 38943 AN: 68294

European-Finnish (FIN) AF: 0.678 AC: 30362 AN: 44774

Middle Eastern (MID) AF: 0.657 AC: 2126 AN: 3234

European-Non Finnish (NFE) AF: 0.609 AC: 504968 AN: 828634

Other (OTH) AF: 0.615 AC: 29431 AN: 47876

GnomAD4 genome AF: 0.610 AC: 92687 AN: 151972 Hom.: 28348 Cov.: 31 AF XY: 0.611 AC XY: 45391 AN XY: 74274

African (AFR) AF: 0.597 AC: 24729 AN: 41452

American (AMR) AF: 0.648 AC: 9890 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2075 AN: 3472

East Asian (EAS) AF: 0.441 AC: 2271 AN: 5148

South Asian (SAS) AF: 0.571 AC: 2750 AN: 4820

European-Finnish (FIN) AF: 0.684 AC: 7234 AN: 10570

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41629 AN: 67936

Other (OTH) AF: 0.624 AC: 1317 AN: 2110

Alfa AF: 0.624 Hom.: 5965

Bravo AF: 0.602

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0020
DANN	Benign	0.66
PhyloP100		-3.6
PromoterAI		-0.020	Neutral
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: rs938350; hg19: chr17-76399552; COSMIC: COSV53145838; COSMIC: COSV53145838;