15-89683665-G-T

Position:

• chr15-89683665-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003847.3(PEX11A):​c.456C>A​(p.Asp152Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PEX11A NM_003847.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.165

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058173686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX11A	NM_003847.3	c.456C>A	p.Asp152Glu	missense_variant	3/3	ENST00000300056.8	NP_003838.1
PEX11A	NM_001271572.2	c.363C>A	p.Asp121Glu	missense_variant	3/3		NP_001258501.1
PEX11A	NM_001271573.2	c.21C>A	p.Asp7Glu	missense_variant	2/2		NP_001258502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX11A	ENST00000300056.8	c.456C>A	p.Asp152Glu	missense_variant	3/3	1	NM_003847.3	ENSP00000300056.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Nov 25, 2024

The c.456C>A (p.D152E) alteration is located in exon 3 (coding exon 3) of the PEX11A gene. This alteration results from a C to A substitution at nucleotide position 456, causing the aspartic acid (D) at amino acid position 152 to be replaced by a glutamic acid (E). 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	0.091
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.8
DANN	Benign	0.57
DEOGEN2	Benign	0.077	T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.51	N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.20	N;N
REVEL	Benign	0.075
Sift	Benign	0.91	T;T
Sift4G	Benign	0.78	T;T
Polyphen		0.0020	B;.
Vest4		0.057
MutPred		0.41		Gain of disorder (P = 0.0992);.;
MVP		0.30
MPC		0.091
ClinPred		0.045	T
GERP RS		3.6
Varity_R		0.058
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr15-90226896;