Variant 11-294577-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025092.5(PGGHG):c.2042G>A(p.Arg681His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,609,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PGGHG
NM_025092.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.608

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029247433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGGHG	NM_025092.5 linkuse as main transcript	c.2042G>A	p.Arg681His	missense_variant	14/14	ENST00000409548.7	NP_079368.3	Q32M88-1A0A024R1Z9
PGGHG	XM_017018355.2 linkuse as main transcript	c.2042G>A	p.Arg681His	missense_variant	14/14		XP_016873844.1	Q32M88-1A0A024R1Z9
PGGHG	XM_011520384.3 linkuse as main transcript	c.1988G>A	p.Arg663His	missense_variant	14/14		XP_011518686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGGHG	ENST00000409548.7 linkuse as main transcript	c.2042G>A	p.Arg681His	missense_variant	14/14	1	NM_025092.5	ENSP00000387185.2		Q32M88-1

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151496

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000285

AC:

AN:

210842

Hom.:

AF XY:

0.0000348

AC XY:

AN XY:

115088

show subpopulations

Gnomad AFR exome

AF:

0.000243

Gnomad AMR exome

AF:

0.0000359

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000395

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1458168

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725216

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000467

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151496

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

73982

show subpopulations

Gnomad4 AFR

AF:

0.000146

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000194

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000165

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

Jun 11, 2021

The c.2042G>A (p.R681H) alteration is located in exon 14 (coding exon 13) of the PGGHG gene. This alteration results from a G to A substitution at nucleotide position 2042, causing the arginine (R) at amino acid position 681 to be replaced by a histidine (H). 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

0.089

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.7

DANN

Benign

0.80

DEOGEN2

Benign

0.020

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.018

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0050

B;B;.

Vest4

0.054

MVP

0.048

MPC

0.15

ClinPred

0.0077

GERP RS

-6.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.017

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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