15-89686451-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003847.3(PEX11A):c.152G>A(p.Ser51Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000424 in 1,414,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: PEX11A NM_003847.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

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]

ACMG classification

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=0.18096673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX11A	NM_003847.3	c.152G>A	p.Ser51Asn	missense_variant	2/3	ENST00000300056.8
PEX11A	NM_001271572.2	c.152G>A	p.Ser51Asn	missense_variant	2/3
PEX11A	NM_001271573.2	c.-263-2503G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX11A	ENST00000300056.8	c.152G>A	p.Ser51Asn	missense_variant	2/3	1	NM_003847.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 250944 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135660

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000424 AC: 6 AN: 1414200 Hom.: 0 Cov.: 25 AF XY: 0.00000708 AC XY: 5 AN XY: 706704

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.36e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.152G>A (p.S51N) alteration is located in exon 2 (coding exon 2) of the PEX11A gene. This alteration results from a G to A substitution at nucleotide position 152, causing the serine (S) at amino acid position 51 to be replaced by an asparagine (N). 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	0.27
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	19
Dann	Benign	0.97
DEOGEN2	Benign	0.0048	T;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.026
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.94	D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.21	N;N;N
Sift	Benign	0.65	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.22	.;B;.
Vest4		0.26
MutPred		0.54		Loss of phosphorylation at S51 (P = 0.0438);Loss of phosphorylation at S51 (P = 0.0438);Loss of phosphorylation at S51 (P = 0.0438);
MVP		0.64
MPC		0.17
ClinPred		0.14	T
GERP RS		4.9
Varity_R		0.15
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs1485468644; hg19: chr15-90229682;