Genetic Variant GNE:c.51+34T>A (chr9-36276860-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001128227.3(GNE):c.51+34T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GNE
NM_001128227.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Publications

5 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:

LOC124902150 (HGNC:):

LOC124902150 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GNE	NM_001128227.3 link	c.51+34T>A	intron_variant	Intron 1 of 11	ENST00000396594.8	NP_001121699.1
GNE	NM_001190388.2 link	c.-14+34T>A	intron_variant	Intron 1 of 10		NP_001177317.2
GNE	XM_005251334.5 link	c.51+34T>A	intron_variant	Intron 1 of 10		XP_005251391.1
LOC124902150	XR_007061473.1 link	n.297-7848A>T	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
GNE	ENST00000396594.8 link	c.51+34T>A	intron_variant	Intron 1 of 11	1	NM_001128227.3	ENSP00000379839.3
GNE	ENST00000543356.7 link	c.-14+34T>A	intron_variant	Intron 1 of 10	1		ENSP00000437765.3
CLTA	ENST00000464497.5 link	n.*101+11286A>T	intron_variant	Intron 6 of 7	5		ENSP00000419158.1
GNE	ENST00000644762.1 link	n.83+34T>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151962

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1367800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

684164

African (AFR)

AF:

0.00

AC:

AN:

30818

American (AMR)

AF:

0.00

AC:

AN:

40198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25368

East Asian (EAS)

AF:

0.00

AC:

AN:

38262

South Asian (SAS)

AF:

0.00

AC:

AN:

79372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5594

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1037548

Other (OTH)

AF:

0.00

AC:

AN:

57394

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151962

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74208

African (AFR)

AF:

0.00

AC:

AN:

41366

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2092

Alfa

AF:

0.00

Hom.:

8402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.050

(source)

DANN

Benign

0.70

PhyloP100

-1.8

PromoterAI

-0.024

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over