9-36215168-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001128227.3(GNE):c.*2196_*2197insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 150,698 control chromosomes in the GnomAD database, including 124 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNE NM_001128227.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.510

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-36215168-C-CA is Benign according to our data. Variant chr9-36215168-C-CA is described in ClinVar as [Benign]. Clinvar id is 366807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNE	NM_001128227.3	c.*2196_*2197insT		3_prime_UTR_variant	12/12	ENST00000396594.8
GNE	NM_005476.7	c.*2196_*2197insT		3_prime_UTR_variant	12/12	ENST00000642385.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNE	ENST00000396594.8	c.*2196_*2197insT		3_prime_UTR_variant	12/12	1	NM_001128227.3
GNE	ENST00000642385.2	c.*2196_*2197insT		3_prime_UTR_variant	12/12		NM_005476.7	P1
CLTA	ENST00000464497.5	c.485+10998dup		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3692 AN: 150584 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.00725

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0233

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 22

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0245 AC: 3690 AN: 150698 Hom.: 124 Cov.: 32 AF XY: 0.0264 AC XY: 1939 AN XY: 73532

Gnomad4 AFR AF: 0.00470

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.00725

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.0588

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0226

Bravo AF: 0.0288

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Sialuria Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

GNE myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Inclusion Body Myopathy, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs199874473; hg19: chr9-36215165;