chr11-292060-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_025092.5(PGGHG):c.991G>A(p.Gly331Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00117 in 1,585,346 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 4 hom. )
Consequence
PGGHG
NM_025092.5 missense
NM_025092.5 missense
Scores
1
10
7
Clinical Significance
Conservation
PhyloP100: 7.20
Genes affected
PGGHG (HGNC:26210): (protein-glucosylgalactosylhydroxylysine glucosidase) Enables protein-glucosylgalactosylhydroxylysine glucosidase activity. Involved in carbohydrate metabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.07723874).
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGGHG | NM_025092.5 | c.991G>A | p.Gly331Arg | missense_variant | 5/14 | ENST00000409548.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGGHG | ENST00000409548.7 | c.991G>A | p.Gly331Arg | missense_variant | 5/14 | 1 | NM_025092.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000815 AC: 124AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000925 AC: 182AN: 196818Hom.: 0 AF XY: 0.000776 AC XY: 82AN XY: 105718
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GnomAD4 exome AF: 0.00120 AC: 1724AN: 1433108Hom.: 4 Cov.: 31 AF XY: 0.00116 AC XY: 826AN XY: 710136
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GnomAD4 genome AF: 0.000815 AC: 124AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 63AN XY: 74438
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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 | Jul 14, 2021 | The c.991G>A (p.G331R) alteration is located in exon 5 (coding exon 4) of the PGGHG gene. This alteration results from a G to A substitution at nucleotide position 991, causing the glycine (G) at amino acid position 331 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;T;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.057);.;Gain of MoRF binding (P = 0.057);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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