chr9-36246500-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001128227.3(GNE):c.258-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000652 in 1,577,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 0 hom. )

Consequence

GNE
NM_001128227.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.496

Publications

0 publications found

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:

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-36246500-T-C is Benign according to our data. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-36246500-T-C is described in CliVar as Likely_benign. Clinvar id is 257525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNE	NM_001128227.3 link	c.258-18A>G		intron_variant	Intron 2 of 11	ENST00000396594.8	NP_001121699.1	Q9Y223-2
GNE	NM_005476.7 link	c.165-18A>G		intron_variant	Intron 2 of 11	ENST00000642385.2	NP_005467.1	Q9Y223-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNE	ENST00000396594.8 link	c.258-18A>G		intron_variant	Intron 2 of 11	1	NM_001128227.3	ENSP00000379839.3		Q9Y223-2
GNE	ENST00000642385.2 link	c.165-18A>G		intron_variant	Intron 2 of 11		NM_005476.7	ENSP00000494141.2		Q9Y223-1

Frequencies

GnomAD3 genomes

AF:

0.000369

AC:

AN:

151764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000380

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000265

AC:

AN:

244986

AF XY:

0.000247

show subpopulations

Gnomad AFR exome

AF:

0.0000663

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000377

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000682

AC:

973

AN:

1426140

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

460

AN XY:

711878

show subpopulations

African (AFR)

AF:

0.0000609

AC:

AN:

32832

American (AMR)

AF:

0.0000896

AC:

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25882

East Asian (EAS)

AF:

0.00

AC:

AN:

39540

South Asian (SAS)

AF:

0.00

AC:

AN:

85460

European-Finnish (FIN)

AF:

0.000327

AC:

AN:

51962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4830

European-Non Finnish (NFE)

AF:

0.000847

AC:

916

AN:

1081916

Other (OTH)

AF:

0.000576

AC:

AN:

59072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000369

AC:

AN:

151764

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

AN XY:

74074

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41284

American (AMR)

AF:

0.0000657

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000380

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000706

AC:

AN:

67954

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.000329

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 21, 2016

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sialuria;C1853926:GNE myopathy

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.3

(source)

DANN

Benign

0.62

PhyloP100

-0.50

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over