chr9-36215539-C-G

Variant names:

• chr9-36215539-C-G
• rs7044157
• NM_001128227.3:c.*1826G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005476.7(GNE):​c.*1826G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,200 control chromosomes in the GnomAD database, including 906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (906 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNE NM_005476.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.371
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-36215539-C-G is Benign according to our data. Variant chr9-36215539-C-G is described in ClinVar as Benign. ClinVar VariationId is 366810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005476.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNE	NM_001128227.3	MANE Plus Clinical	c.*1826G>C		3_prime_UTR	Exon 12 of 12	NP_001121699.1	Q9Y223-2
	GNE	NM_005476.7	MANE Select	c.*1826G>C		3_prime_UTR	Exon 12 of 12	NP_005467.1	Q9Y223-1
	GNE	NM_001374797.1		c.*1826G>C		3_prime_UTR	Exon 11 of 11	NP_001361726.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNE	ENST00000396594.8	TSL:1 MANE Plus Clinical	c.*1826G>C		3_prime_UTR	Exon 12 of 12	ENSP00000379839.3	Q9Y223-2
	GNE	ENST00000642385.2	MANE Select	c.*1826G>C		3_prime_UTR	Exon 12 of 12	ENSP00000494141.2	Q9Y223-1
	CLTA	ENST00000464497.5	TSL:5	n.485+11360C>G		intron	N/A	ENSP00000419158.1	F8WF69

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15929 AN: 152082 Hom.: 901 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.118

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.105 AC: 15949 AN: 152200 Hom.: 906 Cov.: 32 AF XY: 0.106 AC XY: 7852 AN XY: 74410

African (AFR) AF: 0.131 AC: 5425 AN: 41504

American (AMR) AF: 0.0771 AC: 1179 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 330 AN: 3470

East Asian (EAS) AF: 0.174 AC: 900 AN: 5182

South Asian (SAS) AF: 0.146 AC: 703 AN: 4826

European-Finnish (FIN) AF: 0.0741 AC: 786 AN: 10602

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0924 AC: 6287 AN: 68010

Other (OTH) AF: 0.118 AC: 250 AN: 2112

Alfa AF: 0.0885 Hom.: 92

Bravo AF: 0.105

Asia WGS AF: 0.180 AC: 622 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	GNE myopathy (1)
-	-	1	Inclusion Body Myopathy, Recessive (1)
-	-	1	not provided (1)
-	-	1	Sialuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.98
DANN	Benign	0.64
PhyloP100		-0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7044157; hg19: chr9-36215536; COSMIC: COSV54255719; COSMIC: COSV54255719;