chr10-68296284-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_022129.4(PBLD):c.265G>C(p.Val89Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00092 in 1,613,164 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00097 ( 5 hom. )
Consequence
PBLD
NM_022129.4 missense
NM_022129.4 missense
Scores
2
9
7
Clinical Significance
Conservation
PhyloP100: 5.88
Genes affected
PBLD (HGNC:23301): (phenazine biosynthesis like protein domain containing) Enables identical protein binding activity. Involved in maintenance of gastrointestinal epithelium; negative regulation of SMAD protein signal transduction; and negative regulation of transforming growth factor beta receptor signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PBLD | NM_022129.4 | c.265G>C | p.Val89Leu | missense_variant | 4/10 | ENST00000358769.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PBLD | ENST00000358769.7 | c.265G>C | p.Val89Leu | missense_variant | 4/10 | 5 | NM_022129.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000441 AC: 67AN: 152066Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000443 AC: 111AN: 250846Hom.: 1 AF XY: 0.000531 AC XY: 72AN XY: 135630
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GnomAD4 exome AF: 0.000970 AC: 1417AN: 1461098Hom.: 5 Cov.: 31 AF XY: 0.000947 AC XY: 688AN XY: 726880
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GnomAD4 genome ? AF: 0.000441 AC: 67AN: 152066Hom.: 0 Cov.: 33 AF XY: 0.000377 AC XY: 28AN XY: 74278
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2022 | The c.265G>C (p.V89L) alteration is located in exon 4 (coding exon 3) of the PBLD gene. This alteration results from a G to C substitution at nucleotide position 265, causing the valine (V) at amino acid position 89 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;.
Sift4G
Uncertain
D;D;D;D
Polyphen
0.99
.;D;D;.
Vest4
MutPred
0.80
.;Loss of methylation at K93 (P = 0.1105);Loss of methylation at K93 (P = 0.1105);Loss of methylation at K93 (P = 0.1105);
MVP
MPC
0.67
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at