Menu
GeneBe

rs662

chr7-95308134-T-Achr7-95308134-T-Cchr7-95308134-T-G

Variant summary

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

The NM_000446(PON1):c.575A>T(p.Gln192Leu) 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. 14/20 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. Q192R) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Consequence

PON1
NM_000446 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.954

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 31.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.09187052).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PON1NM_000446.7 linkuse as main transcriptc.575A>T p.Gln192Leu missense_variant 6/9 ENST00000222381.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PON1ENST00000222381.8 linkuse as main transcriptc.575A>T p.Gln192Leu missense_variant 6/91 NM_000446.7 P1
PON1ENST00000433729.1 linkuse as main transcriptc.*300A>T 3_prime_UTR_variant, NMD_transcript_variant 6/93

Frequencies

GnomAD3 genomes
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
1.4
Dann
Benign
0.92
DEOGEN2
Benign
0.10
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.046
N
LIST_S2
Benign
0.15
T
M_CAP
Benign
0.0096
T
MetaRNN
Benign
0.092
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.032
Sift
Benign
0.095
T
Sift4G
Benign
0.095
T
Polyphen
0.0
B
Vest4
0.14
MutPred
0.52
Gain of sheet (P = 0.0344);
MVP
0.20
MPC
0.16
ClinPred
0.12
T
GERP RS
-1.0
Varity_R
0.056
gMVP
0.75

Splicing

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.

Other links and lift over

dbSNP: rs662; hg19: chr7-94937446;