Genetic Variant PGS1:c.881-97G>A (chr17-78403471-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.58

Publications

14 publications found

Variant links:

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]

PGS1 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024419.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PGS1	NM_024419.5	MANE Select	c.881-97G>A	intron	N/A	NP_077733.3
PGS1	NR_110601.2		n.820-97G>A	intron	N/A
PGS1	NR_110602.2		n.782-97G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PGS1	ENST00000262764.11	TSL:1 MANE Select	c.881-97G>A	intron	N/A	ENSP00000262764.5
PGS1	ENST00000592043.5	TSL:1	c.875-97G>A	intron	N/A	ENSP00000466219.1
PGS1	ENST00000588281.5	TSL:1	n.429-97G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.610

AC:

92631

AN:

151854

Hom.:

28331

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

13733

27466

41199

54932

68665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12658

25316

37974

50632

63290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.610

AC:

92687

AN:

151972

Hom.:

28348

Cov.:

AF XY:

0.611

AC XY:

45391

AN XY:

74274

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1890

3779

5669

7558

9448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0020

(source)

DANN

Benign

0.66

PhyloP100

-3.6

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over