chr9-36214974-G-A

Variant names:

• chr9-36214974-G-A
• rs1043313
• NM_001128227.3:c.*2391C>T

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.*2391C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,092 control chromosomes in the GnomAD database, including 38,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (38619 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GNE NM_005476.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.04
• Publications: 6 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=-0.81).
• BP6: Variant 9-36214974-G-A is Benign according to our data. Variant chr9-36214974-G-A is described in ClinVar as Benign. ClinVar VariationId is 366804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 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.*2391C>T		3_prime_UTR	Exon 12 of 12	NP_001121699.1	Q9Y223-2
	GNE	NM_005476.7	MANE Select	c.*2391C>T		3_prime_UTR	Exon 12 of 12	NP_005467.1	Q9Y223-1
	GNE	NM_001374797.1		c.*2391C>T		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.*2391C>T		3_prime_UTR	Exon 12 of 12	ENSP00000379839.3	Q9Y223-2
	GNE	ENST00000642385.2	MANE Select	c.*2391C>T		3_prime_UTR	Exon 12 of 12	ENSP00000494141.2	Q9Y223-1
	CLTA	ENST00000464497.5	TSL:5	n.485+10795G>A		intron	N/A	ENSP00000419158.1	F8WF69

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107135 AN: 151974 Hom.: 38589 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.688

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.705 AC: 107222 AN: 152092 Hom.: 38619 Cov.: 32 AF XY: 0.696 AC XY: 51756 AN XY: 74368

African (AFR) AF: 0.712 AC: 29507 AN: 41464

American (AMR) AF: 0.623 AC: 9522 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2180 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1550 AN: 5172

South Asian (SAS) AF: 0.507 AC: 2449 AN: 4828

European-Finnish (FIN) AF: 0.726 AC: 7677 AN: 10570

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51948 AN: 67998

Other (OTH) AF: 0.688 AC: 1451 AN: 2108

Alfa AF: 0.736 Hom.: 171677

Bravo AF: 0.698

Asia WGS AF: 0.460 AC: 1601 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	GNE myopathy (1)
-	-	1	Inclusion Body Myopathy, Recessive (1)
-	-	1	Sialuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		1.0
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: rs1043313; hg19: chr9-36214971;