1-145912181-A-G

Position:

• chr1-145912181-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.760T>C​(p.Trp254Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000824 in 1,456,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: PEX11B NM_003846.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.01

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=0.3691353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX11B	NM_003846.3	c.760T>C	p.Trp254Arg	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.760T>C	p.Trp254Arg	missense_variant	4/4	1	NM_003846.3	ENSP00000358312.3
PEX11B	ENST00000537888.1	c.718T>C	p.Trp240Arg	missense_variant	4/4	2		ENSP00000437510.1
PEX11B	ENST00000428634.1	c.226T>C	p.Trp76Arg	missense_variant	1/2	2		ENSP00000414018.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000824 AC: 12 AN: 1456640 Hom.: 0 Cov.: 31 AF XY: 0.00000966 AC XY: 7 AN XY: 724292

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

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

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 24, 2024

The c.760T>C (p.W254R) alteration is located in exon 4 (coding exon 4) of the PEX11B gene. This alteration results from a T to C substitution at nucleotide position 760, causing the tryptophan (W) at amino acid position 254 to be replaced by an arginine (R). 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	Pathogenic	0.87
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.19	.;T;.
LIST_S2	Benign	0.67	T;T;T
MetaRNN	Benign	0.37	T;T;T
PROVEAN	Benign	-0.93	N;N;N
Sift	Benign	0.52	T;T;T
Sift4G	Benign	0.38	T;T;T
Vest4		0.69, 0.67
gMVP		0.96

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: chr1-145522899;