rs7875447

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001128227.3(GNE):c.51+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,517,118 control chromosomes in the GnomAD database, including 456,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43298 hom., cov: 31)

Exomes 𝑓: 0.77 ( 413309 hom. )

Consequence

GNE
NM_001128227.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.82

Variant links:

Genes affected

GNE (HGNC:23657): (glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase) The protein encoded by this gene is a bifunctional enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. It is a rate-limiting enzyme in the sialic acid biosynthetic pathway. Sialic acid modification of cell surface molecules is crucial for their function in many biologic processes, including cell adhesion and signal transduction. Differential sialylation of cell surface molecules is also implicated in the tumorigenicity and metastatic behavior of malignant cells. Mutations in this gene are associated with sialuria, autosomal recessive inclusion body myopathy, and Nonaka myopathy. Alternative splicing of this gene results in transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GNE links:

LOC124902150 (HGNC:):

LOC124902150 links:

CLTA (HGNC:2090): (clathrin light chain A) Clathrin is a large, soluble protein composed of heavy and light chains. It functions as the main structural component of the lattice-type cytoplasmic face of coated pits and vesicles which entrap specific macromolecules during receptor-mediated endocytosis. This gene encodes one of two clathrin light chain proteins which are believed to function as regulatory elements. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 8 and 12. [provided by RefSeq, May 2010]

CLTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-36276860-A-G is Benign according to our data. Variant chr9-36276860-A-G is described in ClinVar as [Benign]. Clinvar id is 257526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
GNE	NM_001128227.3 linkuse as main transcript	c.51+34T>C	intron_variant	ENST00000396594.8	NP_001121699.1
LOC124902150	XR_007061473.1 linkuse as main transcript	n.297-7848A>G	intron_variant, non_coding_transcript_variant
GNE	NM_001190388.2 linkuse as main transcript	c.-14+34T>C	intron_variant		NP_001177317.2
GNE	XM_005251334.5 linkuse as main transcript	c.51+34T>C	intron_variant		XP_005251391.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
GNE	ENST00000396594.8 linkuse as main transcript	c.51+34T>C	intron_variant	1	NM_001128227.3	ENSP00000379839	Q9Y223-2
GNE	ENST00000543356.7 linkuse as main transcript	c.-14+34T>C	intron_variant	1		ENSP00000437765
CLTA	ENST00000464497.5 linkuse as main transcript	c.*101+11286A>G	intron_variant, NMD_transcript_variant	5		ENSP00000419158
GNE	ENST00000644762.1 linkuse as main transcript	n.83+34T>C	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114022

AN:

151918

Hom.:

43261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.738

Gnomad AMI

AF:

0.884

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.779

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.804

Gnomad OTH

AF:

0.755

GnomAD3 exomes

AF:

0.727

AC:

166817

AN:

229436

Hom.:

61922

AF XY:

0.732

AC XY:

91464

AN XY:

125016

show subpopulations

Gnomad AFR exome

AF:

0.738

Gnomad AMR exome

AF:

0.616

Gnomad ASJ exome

AF:

0.781

Gnomad EAS exome

AF:

0.455

Gnomad SAS exome

AF:

0.684

Gnomad FIN exome

AF:

0.729

Gnomad NFE exome

AF:

0.801

Gnomad OTH exome

AF:

0.758

GnomAD4 exome

AF:

0.774

AC:

1057189

AN:

1365082

Hom.:

413309

Cov.:

AF XY:

0.773

AC XY:

527823

AN XY:

682896

show subpopulations

Gnomad4 AFR exome

AF:

0.729

Gnomad4 AMR exome

AF:

0.623

Gnomad4 ASJ exome

AF:

0.780

Gnomad4 EAS exome

AF:

0.464

Gnomad4 SAS exome

AF:

0.687

Gnomad4 FIN exome

AF:

0.733

Gnomad4 NFE exome

AF:

0.803

Gnomad4 OTH exome

AF:

0.757

GnomAD4 genome

AF:

0.751

AC:

114115

AN:

152036

Hom.:

43298

Cov.:

AF XY:

0.743

AC XY:

55249

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.737

Gnomad4 AMR

AF:

0.682

Gnomad4 ASJ

AF:

0.779

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.716

Gnomad4 NFE

AF:

0.804

Gnomad4 OTH

AF:

0.758

Alfa

AF:

0.777

Hom.:

8182

Bravo

AF:

0.745

Asia WGS

AF:

0.618

AC:

2150

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 30, 2021	- -

GNE myopathy

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Jan 03, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Sialuria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.052

DANN

Benign

0.68

Splicing

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