rs16933102

Variant names:

• chr9-36227204-C-T
• rs16933102
• NM_001128227.3:c.1374+44G>A

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.1281+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,230,326 control chromosomes in the GnomAD database, including 374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (201 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (173 hom.)
• Consequence: GNE NM_005476.7 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.143
• 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=-0.88).
• BP6: Variant 9-36227204-C-T is Benign according to our data. Variant chr9-36227204-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0913 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.1374+44G>A		intron	N/A	NP_001121699.1	Q9Y223-2
	GNE	NM_005476.7	MANE Select	c.1281+44G>A		intron	N/A	NP_005467.1	Q9Y223-1
	GNE	NM_001374797.1		c.1128+44G>A		intron	N/A	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.1374+44G>A		intron	N/A	ENSP00000379839.3	Q9Y223-2
	GNE	ENST00000642385.2	MANE Select	c.1281+44G>A		intron	N/A	ENSP00000494141.2	Q9Y223-1
	GNE	ENST00000543356.7	TSL:1	c.1104+44G>A		intron	N/A	ENSP00000437765.3	A0A7I2SU25

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4308 AN: 152034 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0938

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.00871 AC: 2136 AN: 245300 AF XY: 0.00711

Gnomad AFR exome AF: 0.0953

Gnomad AMR exome AF: 0.00820

Gnomad ASJ exome AF: 0.00569

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.00651

GnomAD4 exome AF: 0.00427 AC: 4606 AN: 1078174 Hom.: 173 Cov.: 15 AF XY: 0.00409 AC XY: 2265 AN XY: 553846

African (AFR) AF: 0.0982 AC: 2533 AN: 25782

American (AMR) AF: 0.00839 AC: 369 AN: 43972

Ashkenazi Jewish (ASJ) AF: 0.00594 AC: 140 AN: 23562

East Asian (EAS) AF: 0.0000264 AC: 1 AN: 37902

South Asian (SAS) AF: 0.00600 AC: 468 AN: 77978

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53068

Middle Eastern (MID) AF: 0.0127 AC: 64 AN: 5046

European-Non Finnish (NFE) AF: 0.000803 AC: 613 AN: 763146

Other (OTH) AF: 0.00874 AC: 417 AN: 47718

GnomAD4 genome AF: 0.0284 AC: 4316 AN: 152152 Hom.: 201 Cov.: 32 AF XY: 0.0275 AC XY: 2049 AN XY: 74382

African (AFR) AF: 0.0938 AC: 3891 AN: 41496

American (AMR) AF: 0.0159 AC: 243 AN: 15282

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

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

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4820

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10578

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

European-Non Finnish (NFE) AF: 0.00110 AC: 75 AN: 68000

Other (OTH) AF: 0.0242 AC: 51 AN: 2110

Alfa AF: 0.0208 Hom.: 50

Bravo AF: 0.0329

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		0.14
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: rs16933102; hg19: chr9-36227201; COSMIC: COSV64953490;