11-289829-G-C

Position:

• chr11-289829-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025092.5(PGGHG):​c.13G>C​(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: PGGHG NM_025092.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.687

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]

ACMG classification

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=0.058196396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGGHG	NM_025092.5	c.13G>C	p.Gly5Arg	missense_variant	2/14	ENST00000409548.7	NP_079368.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGGHG	ENST00000409548.7	c.13G>C	p.Gly5Arg	missense_variant	2/14	1	NM_025092.5	ENSP00000387185.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 28, 2021

The c.13G>C (p.G5R) alteration is located in exon 2 (coding exon 1) of the PGGHG gene. This alteration results from a G to C substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 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	0.083
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.14
DANN	Benign	0.72
DEOGEN2	Benign	0.0065	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.14	N;N
REVEL	Benign	0.22
Sift	Benign	0.26	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.33	B;P
Vest4		0.21
MutPred		0.13		Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);
MVP		0.092
MPC		0.30
ClinPred		0.17	T
GERP RS		-7.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.052
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-289829;