chr20-33710737-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_007238.5(PXMP4):ā€‹c.193T>Cā€‹(p.Trp65Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,457,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

PXMP4
NM_007238.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0490
Variant links:
Genes affected
PXMP4 (HGNC:15920): (peroxisomal membrane protein 4) Located in peroxisomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.020771176).
BP6
Variant 20-33710737-A-G is Benign according to our data. Variant chr20-33710737-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2524934.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PXMP4NM_007238.5 linkuse as main transcriptc.193T>C p.Trp65Arg missense_variant 3/4 ENST00000409299.8
PXMP4NM_183397.3 linkuse as main transcriptc.177-2768T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PXMP4ENST00000409299.8 linkuse as main transcriptc.193T>C p.Trp65Arg missense_variant 3/41 NM_007238.5 P1Q9Y6I8-1
PXMP4ENST00000217398.3 linkuse as main transcriptc.213T>C p.Cys71= synonymous_variant 3/42
PXMP4ENST00000344022.7 linkuse as main transcriptc.177-2768T>C intron_variant 2 Q9Y6I8-2

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000817
AC:
2
AN:
244758
Hom.:
0
AF XY:
0.00000753
AC XY:
1
AN XY:
132760
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000294
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000917
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000618
AC:
9
AN:
1457078
Hom.:
0
Cov.:
33
AF XY:
0.00000966
AC XY:
7
AN XY:
724372
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
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:
0.00000451
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
Cov.:
30
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 04, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.047
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
4.8
DANN
Benign
0.61
DEOGEN2
Benign
0.029
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.021
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-1.5
N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
2.3
N
REVEL
Benign
0.038
Sift
Benign
1.0
T
Sift4G
Benign
0.73
T
Polyphen
0.0
B
Vest4
0.071
MutPred
0.42
Gain of methylation at W65 (P = 0.0293);
MVP
0.043
MPC
0.90
ClinPred
0.070
T
GERP RS
0.35
Varity_R
0.021
gMVP
0.48

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.

Other links and lift over

dbSNP: rs781582757; hg19: chr20-32298543; API