1-145912184-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003846.3(PEX11B):​c.757C>A​(p.Pro253Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PEX11B
NM_003846.3 missense

Scores

6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.42
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PEX11BNM_003846.3 linkuse as main transcriptc.757C>A p.Pro253Thr missense_variant 4/4 ENST00000369306.8 NP_003837.1 O96011-1A0A024R4E7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PEX11BENST00000369306.8 linkuse as main transcriptc.757C>A p.Pro253Thr missense_variant 4/41 NM_003846.3 ENSP00000358312.3 O96011-1
PEX11BENST00000537888.1 linkuse as main transcriptc.715C>A p.Pro239Thr missense_variant 4/42 ENSP00000437510.1 O96011-2
PEX11BENST00000428634.1 linkuse as main transcriptc.223C>A p.Pro75Thr missense_variant 1/22 ENSP00000414018.1 H7C3V6

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1457584
Hom.:
0
Cov.:
31
AF XY:
0.00000414
AC XY:
3
AN XY:
724858
show subpopulations
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 21, 2023The c.757C>A (p.P253T) alteration is located in exon 4 (coding exon 4) of the PEX11B gene. This alteration results from a C to A substitution at nucleotide position 757, causing the proline (P) at amino acid position 253 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
Pathogenic
0.84
BayesDel_noAF
Pathogenic
0.45
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.74
.;D;.
LIST_S2
Uncertain
0.94
D;D;D
MetaRNN
Pathogenic
0.82
D;D;D
PROVEAN
Pathogenic
-7.3
D;D;D
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Vest4
0.79, 0.79
gMVP
0.99

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: chr1-145522896; API