rs7875447

Variant names:

• chr9-36276860-A-G
• rs7875447
• NM_001128227.3:c.51+34T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-36276860-A-G
• chr9-36276860-A-T

Variant summary

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

The NM_001128227.3(GNE):​c.51+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,517,118 control chromosomes in the GnomAD database, including 456,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43298 hom., cov: 31)
  • Exomes 𝑓: 0.77 (413309 hom.)
• Consequence: GNE NM_001128227.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.82
• Publications: 5 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]

LOC124902150 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-36276860-A-G is Benign according to our data. Variant chr9-36276860-A-G is described in ClinVar as Benign. ClinVar VariationId is 257526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNE	NM_001128227.3	c.51+34T>C		intron_variant	Intron 1 of 11	ENST00000396594.8	NP_001121699.1
GNE	NM_001190388.2	c.-14+34T>C		intron_variant	Intron 1 of 10		NP_001177317.2
GNE	XM_005251334.5	c.51+34T>C		intron_variant	Intron 1 of 10		XP_005251391.1
LOC124902150	XR_007061473.1	n.297-7848A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNE	ENST00000396594.8	c.51+34T>C		intron_variant	Intron 1 of 11	1	NM_001128227.3	ENSP00000379839.3
GNE	ENST00000543356.7	c.-14+34T>C		intron_variant	Intron 1 of 10	1		ENSP00000437765.3
CLTA	ENST00000464497.5	n.*101+11286A>G		intron_variant	Intron 6 of 7	5		ENSP00000419158.1
GNE	ENST00000644762.1	n.83+34T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114022 AN: 151918 Hom.: 43261 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.755

GnomAD2 exomes AF: 0.727 AC: 166817 AN: 229436 AF XY: 0.732

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.616

Gnomad ASJ exome AF: 0.781

Gnomad EAS exome AF: 0.455

Gnomad FIN exome AF: 0.729

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.758

GnomAD4 exome AF: 0.774 AC: 1057189 AN: 1365082 Hom.: 413309 Cov.: 20 AF XY: 0.773 AC XY: 527823 AN XY: 682896

African (AFR) AF: 0.729 AC: 22423 AN: 30760

American (AMR) AF: 0.623 AC: 25001 AN: 40158

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 19751 AN: 25326

East Asian (EAS) AF: 0.464 AC: 17750 AN: 38220

South Asian (SAS) AF: 0.687 AC: 54423 AN: 79248

European-Finnish (FIN) AF: 0.733 AC: 39042 AN: 53232

Middle Eastern (MID) AF: 0.748 AC: 4181 AN: 5590

European-Non Finnish (NFE) AF: 0.803 AC: 831231 AN: 1035262

Other (OTH) AF: 0.757 AC: 43387 AN: 57286

GnomAD4 genome AF: 0.751 AC: 114115 AN: 152036 Hom.: 43298 Cov.: 31 AF XY: 0.743 AC XY: 55249 AN XY: 74310

African (AFR) AF: 0.737 AC: 30581 AN: 41472

American (AMR) AF: 0.682 AC: 10415 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2706 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2413 AN: 5170

South Asian (SAS) AF: 0.660 AC: 3182 AN: 4820

European-Finnish (FIN) AF: 0.716 AC: 7545 AN: 10536

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54670 AN: 67984

Other (OTH) AF: 0.758 AC: 1601 AN: 2112

Alfa AF: 0.777 Hom.: 8402

Bravo AF: 0.745

Asia WGS AF: 0.618 AC: 2150 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 30, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GNE myopathy Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 03, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Sialuria Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.052
DANN	Benign	0.68
PhyloP100		-1.8
PromoterAI		-0.0027	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7875447; hg19: chr9-36276857; COSMIC: COSV67454188;