Variant 11-290888-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_025092.5(PGGHG):c.681G>A(p.Leu227Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 1,611,932 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 60 hom. )

Consequence

PGGHG
NM_025092.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.07

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 Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 11-290888-G-A is Benign according to our data. Variant chr11-290888-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3341523.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.07 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00674 (9838/1459632) while in subpopulation MID AF= 0.0207 (119/5742). AF 95% confidence interval is 0.0177. There are 60 homozygotes in gnomad4_exome. There are 5041 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGGHG	NM_025092.5 linkuse as main transcript	c.681G>A	p.Leu227Leu	synonymous_variant	4/14	ENST00000409548.7	NP_079368.3	Q32M88-1A0A024R1Z9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGGHG	ENST00000409548.7 linkuse as main transcript	c.681G>A	p.Leu227Leu	synonymous_variant	4/14	1	NM_025092.5	ENSP00000387185.2		Q32M88-1

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

838

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00582

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00742

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00700

AC:

1745

AN:

249364

Hom.:

AF XY:

0.00762

AC XY:

1030

AN XY:

135162

show subpopulations

Gnomad AFR exome

AF:

0.000868

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.0186

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.00949

Gnomad FIN exome

AF:

0.00585

Gnomad NFE exome

AF:

0.00855

Gnomad OTH exome

AF:

0.00806

GnomAD4 exome

AF:

0.00674

AC:

9838

AN:

1459632

Hom.:

Cov.:

AF XY:

0.00694

AC XY:

5041

AN XY:

726056

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00359

Gnomad4 ASJ exome

AF:

0.0169

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00933

Gnomad4 FIN exome

AF:

0.00639

Gnomad4 NFE exome

AF:

0.00674

Gnomad4 OTH exome

AF:

0.00746

GnomAD4 genome

AF:

0.00550

AC:

837

AN:

152300

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

437

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00581

Gnomad4 ASJ

AF:

0.0208

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00911

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.00741

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00737

Hom.:

Bravo

AF:

0.00513

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00960

EpiControl

AF:

0.00996

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

PGGHG: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.64

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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