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GeneBe

rs854560

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

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.197

Links

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
PON1NM_000446.7 linkuse as main transcriptc.163T>G p.Leu55Val missense_variant 3/9 ENST00000222381.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PON1ENST00000222381.8 linkuse as main transcriptc.163T>G p.Leu55Val missense_variant 3/91 NM_000446.7 P1
PON1ENST00000470502.1 linkuse as main transcriptn.283T>G non_coding_transcript_exon_variant 2/44
PON1ENST00000433729.1 linkuse as main transcriptc.163T>G p.Leu55Val missense_variant, NMD_transcript_variant 3/93

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460752
Hom.:
0
AF XY:
0.00000138
AC XY:
1
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
T
BayesDel_noAF
Benign
-0.51
Cadd
Benign
16
Dann
Uncertain
0.98
DEOGEN2
Benign
0.081
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.0096
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
0.55
D;D
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.42
N
REVEL
Benign
0.085
Sift
Benign
0.082
T
Sift4G
Uncertain
0.058
T
Polyphen
0.0
B
Vest4
0.17
MutPred
0.33
Loss of disorder (P = 0.1309);
MVP
0.26
MPC
0.15
ClinPred
0.59
D
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.

Other links and lift over

dbSNP: rs854560; hg19: chr7-94946084;