15-89683403-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003847.3(PEX11A):c.718C>A(p.Pro240Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PEX11A NM_003847.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.01

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX11A	NM_003847.3	c.718C>A	p.Pro240Thr	missense_variant	3/3	ENST00000300056.8
PEX11A	NM_001271572.2	c.625C>A	p.Pro209Thr	missense_variant	3/3
PEX11A	NM_001271573.2	c.283C>A	p.Pro95Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX11A	ENST00000300056.8	c.718C>A	p.Pro240Thr	missense_variant	3/3	1	NM_003847.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jun 26, 2023

The c.718C>A (p.P240T) 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 718, causing the proline (P) at amino acid position 240 to be replaced by a threonine (T). 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	0.32
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	3.3	M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-7.4	D;D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.81
MutPred		0.82		Gain of MoRF binding (P = 0.0394);.;
MVP		0.95
MPC		0.52
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.84
gMVP		0.79

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: chr15-90226634; COSMIC: COSV55584677; COSMIC: COSV55584677;