Variant 11-292060-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.20

Variant links:

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]

PGGHG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07723874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGGHG	NM_025092.5 linkuse as main transcript	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 linkuse as main transcript	c.991G>A	p.Gly331Arg	missense_variant	5/14	1	NM_025092.5	P1	Q32M88-1

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000925

AC:

182

AN:

196818

Hom.:

AF XY:

0.000776

AC XY:

AN XY:

105718

show subpopulations

Gnomad AFR exome

AF:

0.000167

Gnomad AMR exome

AF:

0.00245

Gnomad ASJ exome

AF:

0.00102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000774

Gnomad FIN exome

AF:

0.000229

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00136

GnomAD4 exome

AF:

0.00120

AC:

1724

AN:

1433108

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

826

AN XY:

710136

show subpopulations

Gnomad4 AFR exome

AF:

0.000302

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00114

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.000218

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.000815

AC:

124

AN:

152238

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00104

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000625

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.20

T;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.077

T;T;T

MetaSVM

Uncertain

-0.16

MutationTaster

Benign

0.80

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.29

Sift

Uncertain

0.011

D;T;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.80

MutPred

0.61

Gain of MoRF binding (P = 0.057);.;Gain of MoRF binding (P = 0.057);

MVP

0.29

MPC

0.62

ClinPred

0.10

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over