Genetic Variant NM_024419.5:c.14C>G (chr17-78378679-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024419.5(PGS1):c.14C>G(p.Ala5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000954 in 1,531,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00097 ( 0 hom. )

Consequence

PGS1
NM_024419.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.75

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0055626333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGS1	NM_024419.5 link	c.14C>G	p.Ala5Gly	missense_variant	Exon 1 of 10	ENST00000262764.11	NP_077733.3	Q32NB8-1A0A024R8V5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGS1	ENST00000262764.11 link	c.14C>G	p.Ala5Gly	missense_variant	Exon 1 of 10	1	NM_024419.5	ENSP00000262764.5		Q32NB8-1

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00115

AC:

148

AN:

128152

Hom.:

AF XY:

0.00126

AC XY:

AN XY:

71618

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.000357

Gnomad NFE exome

AF:

0.00162

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000968

AC:

1335

AN:

1379408

Hom.:

Cov.:

AF XY:

0.000964

AC XY:

658

AN XY:

682384

show subpopulations

Gnomad4 AFR exome

AF:

0.000175

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.0000413

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.000278

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.000801

GnomAD4 genome

AF:

0.000827

AC:

126

AN:

152324

Hom.:

Cov.:

AF XY:

0.000872

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000446

Hom.:

Bravo

AF:

0.00107

ExAC

AF:

0.000974

AC:

106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.038

T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.31

N;.

REVEL

Benign

0.063

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.25

B;.

Vest4

0.29

MVP

0.26

MPC

0.44

ClinPred

0.23

GERP RS

2.8

Varity_R

0.14

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over