rs854560

chr7-95316772-A-Cchr7-95316772-A-Gchr7-95316772-A-Nchr7-95316772-A-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate

The NM_000446(PON1):c.163T>G(p.Leu55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L55M) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PON1
NM_000446 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.197

Links

PON1 (HGNC:9204):

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant; Number of alleles below threshold, Median coverage is 32.

BP4

Computational evidence support a benign effect (MetaRNN=0.13520142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON1	NM_000446.7 linkuse as main transcript	c.163T>G	p.Leu55Val	missense_variant	3/9	ENST00000222381.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PON1	ENST00000222381.8 linkuse as main transcript	c.163T>G	p.Leu55Val	missense_variant	3/9	1	NM_000446.7	P1
PON1	ENST00000470502.1 linkuse as main transcript	n.283T>G		non_coding_transcript_exon_variant	2/4	4
PON1	ENST00000433729.1 linkuse as main transcript	c.163T>G	p.Leu55Val	missense_variant, NMD_transcript_variant	3/9	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460752

Hom.:

AF XY:

0.00000138

AC XY:

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.081

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.77

M_CAP

Benign

0.0096

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.55

D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

0.42

REVEL

Benign

0.085

Sift

Benign

0.082

Sift4G

Uncertain

0.058

Polyphen

0.0

Vest4

0.17

MutPred

0.33

Loss of disorder (P = 0.1309);

MVP

0.26

MPC

0.15

ClinPred

0.59

GERP RS

-1.8

Varity_R

0.065

gMVP

0.82

Splicing

Find out SpliceAI 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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over