1-145912240-A-G

Position:

• chr1-145912240-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003846.3(PEX11B):​c.701T>C​(p.Ile234Thr) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PEX11B NM_003846.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.89

Genes affected

PEX11B (HGNC:8853): (peroxisomal biogenesis factor 11 beta) The protein encoded by this gene facilitates peroxisomal proliferation and interacts with PEX19. The encoded protein is found in the peroxisomal membrane. Several transcript variants, some protein-coding and some not protein-coding, have been found for this gene. [provided by RefSeq, Dec 2012]

PEX11B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38004318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX11B	NM_003846.3	c.701T>C	p.Ile234Thr	missense_variant	4/4	ENST00000369306.8	NP_003837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX11B	ENST00000369306.8	c.701T>C	p.Ile234Thr	missense_variant	4/4	1	NM_003846.3	ENSP00000358312.3
PEX11B	ENST00000537888.1	c.659T>C	p.Ile220Thr	missense_variant	4/4	2		ENSP00000437510.1
PEX11B	ENST00000428634.1	c.167T>C	p.Ile56Thr	missense_variant	1/2	2		ENSP00000414018.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2022

ClinVar contains an entry for this variant (Variation ID: 1441988). This variant has not been reported in the literature in individuals affected with PEX11B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 234 of the PEX11B protein (p.Ile234Thr). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.97
DEOGEN2	Benign	0.11	.;T;.
LIST_S2	Uncertain	0.91	D;D;D
MetaRNN	Benign	0.38	T;T;T
PROVEAN	Benign	-0.48	N;N;N
Sift	Benign	0.34	T;D;D
Sift4G	Benign	0.14	T;T;T
Vest4		0.33, 0.34
gMVP		0.92

Splicing

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: chr1-145522840;