dbSNP rs373673442: PEX11A:p.Arg6Leu (chr15-89690616-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003847.3(PEX11A):c.17G>T(p.Arg6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R6H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

PEX11A
NM_003847.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.919

Publications

0 publications found

Variant links:

Genes affected

PEX11A (HGNC:8852): (peroxisomal biogenesis factor 11 alpha) This gene is a member of the PEX11 family, which is composed of membrane elongation factors involved in regulation of peroxisome maintenance and proliferation. This gene product interacts with peroxisomal membrane protein 19 and may respond to outside stimuli to increase peroxisome abundance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

PEX11A links:

WDR93 (HGNC:26924): (WD repeat domain 93) Predicted to enable oxidoreductase activity, acting on NAD(P)H. Predicted to be involved in electron transport chain. Predicted to be part of mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

WDR93 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

WDR93 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36980498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX11A	NM_003847.3 link	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 3	ENST00000300056.8	NP_003838.1	O75192-1B2R8C6
WDR93	NM_020212.2 link	c.-282C>A		upstream_gene_variant		ENST00000268130.12	NP_064597.1	Q6P2C0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX11A	ENST00000300056.8 link	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 3	1	NM_003847.3	ENSP00000300056.3		O75192-1
WDR93	ENST00000268130.12 link	c.-282C>A		upstream_gene_variant		1	NM_020212.2	ENSP00000268130.7		Q6P2C0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399002

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31590

American (AMR)

AF:

0.00

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35728

South Asian (SAS)

AF:

0.00

AC:

AN:

79226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.00000371

AC:

AN:

1078850

Other (OTH)

AF:

0.00

AC:

AN:

57982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

T;T;.;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.37

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

.;M;M;.

PhyloP100

0.92

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-4.9

D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0090

D;D;D;.

Sift4G

Benign

0.10

T;T;T;.

Polyphen

0.82

.;P;.;.

Vest4

0.14

MutPred

0.73

Loss of MoRF binding (P = 0.001);Loss of MoRF binding (P = 0.001);Loss of MoRF binding (P = 0.001);Loss of MoRF binding (P = 0.001);

MVP

0.74

MPC

0.25

ClinPred

0.95

GERP RS

4.5

PromoterAI

0.017

Neutral

(source)

Varity_R

0.38

gMVP

0.24

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over