19-7477237-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080662.4(PEX11G):ā€‹c.691C>Gā€‹(p.Arg231Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PEX11G
NM_080662.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.408
Variant links:
Genes affected
PEX11G (HGNC:20208): (peroxisomal biogenesis factor 11 gamma) The protein encoded by this gene is a member of the PEX11 family. This family is reported to regulate the number and size of peroxisomes in evolutionarily distant organisms. The protein encoded by this gene may induce clustering of peroxisomes. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.111210465).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PEX11GNM_080662.4 linkuse as main transcriptc.691C>G p.Arg231Gly missense_variant 5/5 ENST00000221480.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PEX11GENST00000221480.6 linkuse as main transcriptc.691C>G p.Arg231Gly missense_variant 5/51 NM_080662.4 P1Q96HA9-1
PEX11GENST00000593942.5 linkuse as main transcriptc.481C>G p.Arg161Gly missense_variant 7/75 Q96HA9-2
PEX11GENST00000593547.1 linkuse as main transcriptc.472C>G p.Arg158Gly missense_variant 5/55
PEX11GENST00000599519.1 linkuse as main transcriptn.493C>G non_coding_transcript_exon_variant 4/43

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1393004
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
689026
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 29, 2024The c.691C>G (p.R231G) alteration is located in exon 5 (coding exon 5) of the PEX11G gene. This alteration results from a C to G substitution at nucleotide position 691, causing the arginine (R) at amino acid position 231 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
4.4
DANN
Benign
0.70
DEOGEN2
Benign
0.011
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.081
N
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.6
N;.
REVEL
Benign
0.16
Sift
Benign
0.42
T;.
Sift4G
Benign
0.47
T;T
Polyphen
0.0070
B;.
Vest4
0.095
MutPred
0.44
Loss of helix (P = 0.0104);.;
MVP
0.24
MPC
0.061
ClinPred
0.039
T
GERP RS
-6.9
Varity_R
0.046
gMVP
0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-7542123; API