Variant 11-290480-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025092.5(PGGHG):c.350G>A(p.Arg117Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,397,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PGGHG
NM_025092.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.107403874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGGHG	NM_025092.5 linkuse as main transcript	c.350G>A	p.Arg117Gln	missense_variant	3/14	ENST00000409548.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGGHG	ENST00000409548.7 linkuse as main transcript	c.350G>A	p.Arg117Gln	missense_variant	3/14	1	NM_025092.5	P1	Q32M88-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000261

AC:

AN:

153484

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000811

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000338

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1397844

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

689446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000834

Gnomad4 OTH exome

AF:

0.0000518

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000208

AC:

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

Aug 13, 2021

The c.350G>A (p.R117Q) alteration is located in exon 3 (coding exon 2) of the PGGHG gene. This alteration results from a G to A substitution at nucleotide position 350, causing the arginine (R) at amino acid position 117 to be replaced by a glutamine (Q). 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

0.079

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.71

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.046

Sift

Benign

0.11

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0060

B;B

Vest4

0.22

MutPred

0.60

Loss of phosphorylation at S119 (P = 0.1028);Loss of phosphorylation at S119 (P = 0.1028);

MVP

0.095

MPC

0.16

ClinPred

0.12

GERP RS

0.81

Varity_R

0.034

gMVP

0.39

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