Variant 11-294461-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.2003G>A(p.Arg668Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000499 in 1,243,600 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 0.000052 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

PGGHG
NM_025092.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.817

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=0.019589156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PGGHG	NM_025092.5 linkuse as main transcript	c.2003G>A	p.Arg668Gln	missense_variant	13/14	ENST00000409548.7
PGGHG	XM_017018355.2 linkuse as main transcript	c.2003G>A	p.Arg668Gln	missense_variant	13/14
PGGHG	XM_011520384.3 linkuse as main transcript	c.1949G>A	p.Arg650Gln	missense_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGGHG	ENST00000409548.7 linkuse as main transcript	c.2003G>A	p.Arg668Gln	missense_variant	13/14	1	NM_025092.5	P1	Q32M88-1

Frequencies

GnomAD3 genomes

AF:

0.0000523

AC:

AN:

57408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000616

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000181

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:

0.0000396

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

233260

Hom.:

AF XY:

0.0000867

AC XY:

AN XY:

126836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000826

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:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000497

AC:

AN:

1186192

Hom.:

Cov.:

AF XY:

0.0000378

AC XY:

AN XY:

581362

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000817

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000155

Gnomad4 FIN exome

AF:

0.0000714

Gnomad4 NFE exome

AF:

0.0000277

Gnomad4 OTH exome

AF:

0.0000456

GnomAD4 genome

AF:

0.0000523

AC:

AN:

57408

Hom.:

Cov.:

AF XY:

0.0000719

AC XY:

AN XY:

27808

show subpopulations

Gnomad4 AFR

AF:

0.0000616

Gnomad4 AMR

AF:

0.000181

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000396

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000659

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

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

Sep 16, 2021

The c.2003G>A (p.R668Q) alteration is located in exon 13 (coding exon 12) of the PGGHG gene. This alteration results from a G to A substitution at nucleotide position 2003, causing the arginine (R) at amino acid position 668 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

0.089

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Benign

0.91

DEOGEN2

Benign

0.0086

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.65

N;N;N

REVEL

Benign

0.019

Sift

Benign

0.44

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.074

B;P;.

Vest4

0.14

MVP

0.040

MPC

0.14

ClinPred

0.020

GERP RS

-0.27

Varity_R

0.015

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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