15-89683727-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_003847.3(PEX11A):c.394C>G(p.Leu132Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,461,664 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: PEX11A NM_003847.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.18

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25480348).
• BP6: Variant 15-89683727-G-C is Benign according to our data. Variant chr15-89683727-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2645697.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX11A	NM_003847.3	c.394C>G	p.Leu132Val	missense_variant	3/3	ENST00000300056.8
PEX11A	NM_001271572.2	c.301C>G	p.Leu101Val	missense_variant	3/3
PEX11A	NM_001271573.2	c.-42C>G		5_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX11A	ENST00000300056.8	c.394C>G	p.Leu132Val	missense_variant	3/3	1	NM_003847.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000318 AC: 8 AN: 251380 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135846

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1461664 Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28 AN XY: 727128

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: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.0000994

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

PEX11A: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Benign	0.084	T;.
Eigen	Benign	0.037
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.15	N;N
REVEL	Benign	0.10
Sift	Benign	0.28	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.78	P;.
Vest4		0.13
MutPred		0.68		Gain of MoRF binding (P = 0.1743);.;
MVP		0.62
MPC		0.50
ClinPred		0.10	T
GERP RS		4.8
Varity_R		0.091
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749264393; hg19: chr15-90226958;