rs7047950

Variant names:

• chr9-36246047-G-A
• rs7047950
• NM_001128227.3:c.693C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005476.7(GNE):​c.600C>T​(p.Ile200Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,613,574 control chromosomes in the GnomAD database, including 376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (183 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (193 hom.)
• Consequence: GNE NM_005476.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 2.21
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 9-36246047-G-A is Benign according to our data. Variant chr9-36246047-G-A is described in ClinVar as Benign. ClinVar VariationId is 196411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.087 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.693C>T	p.Ile231Ile	synonymous	Exon 3 of 12	NP_001121699.1	Q9Y223-2
	GNE	NM_005476.7	MANE Select	c.600C>T	p.Ile200Ile	synonymous	Exon 3 of 12	NP_005467.1	Q9Y223-1
	GNE	NM_001374797.1		c.600C>T	p.Ile200Ile	synonymous	Exon 3 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.693C>T	p.Ile231Ile	synonymous	Exon 3 of 12	ENSP00000379839.3	Q9Y223-2
	GNE	ENST00000642385.2	MANE Select	c.600C>T	p.Ile200Ile	synonymous	Exon 3 of 12	ENSP00000494141.2	Q9Y223-1
	GNE	ENST00000543356.7	TSL:1	c.423C>T	p.Ile141Ile	synonymous	Exon 2 of 11	ENSP00000437765.3	A0A7I2SU25

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4098 AN: 152226 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00620

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.00843 AC: 2118 AN: 251312 AF XY: 0.00694

Gnomad AFR exome AF: 0.0904

Gnomad AMR exome AF: 0.00755

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00381 AC: 5569 AN: 1461230 Hom.: 193 Cov.: 33 AF XY: 0.00371 AC XY: 2695 AN XY: 726954

African (AFR) AF: 0.0952 AC: 3185 AN: 33464

American (AMR) AF: 0.00787 AC: 352 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00628 AC: 164 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00596 AC: 514 AN: 86248

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53306

Middle Eastern (MID) AF: 0.0113 AC: 65 AN: 5766

European-Non Finnish (NFE) AF: 0.000731 AC: 813 AN: 1111506

Other (OTH) AF: 0.00785 AC: 474 AN: 60382

GnomAD4 genome AF: 0.0270 AC: 4111 AN: 152344 Hom.: 183 Cov.: 32 AF XY: 0.0261 AC XY: 1946 AN XY: 74508

African (AFR) AF: 0.0894 AC: 3716 AN: 41570

American (AMR) AF: 0.0145 AC: 222 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00621 AC: 30 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 68032

Other (OTH) AF: 0.0218 AC: 46 AN: 2114

Alfa AF: 0.0112 Hom.: 107

Bravo AF: 0.0312

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00166

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	GNE myopathy (2)
-	-	1	Inclusion Body Myopathy, Recessive (1)
-	-	1	not provided (1)
-	-	1	Sialuria (1)
-	-	1	Sialuria;C1853926:GNE myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.7
DANN	Benign	0.84
PhyloP100		2.2
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: rs7047950; hg19: chr9-36246044;