rs200763627

Variant names:

• chr9-36276927-A-G
• rs200763627
• NM_001128227.3:c.18T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-36276927-A-G
• chr9-36276927-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001128227.3(GNE):​c.18T>C​(p.Tyr6Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GNE NM_001128227.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.20
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12438473).
• BP6: Variant 9-36276927-A-G is Benign according to our data. Variant chr9-36276927-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1569055.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNE	NM_001128227.3	c.18T>C	p.Tyr6Tyr	synonymous_variant	Exon 1 of 12	ENST00000396594.8	NP_001121699.1
GNE	XM_005251334.5	c.18T>C	p.Tyr6Tyr	synonymous_variant	Exon 1 of 11		XP_005251391.1
GNE	NM_001190388.2	c.-47T>C		5_prime_UTR_variant	Exon 1 of 11		NP_001177317.2
LOC124902150	XR_007061473.1	n.297-7781A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNE	ENST00000396594.8	c.18T>C	p.Tyr6Tyr	synonymous_variant	Exon 1 of 12	1	NM_001128227.3	ENSP00000379839.3
GNE	ENST00000543356.7	c.-47T>C		5_prime_UTR_variant	Exon 1 of 11	1		ENSP00000437765.3
GNE	ENST00000644762.1	n.50T>C		non_coding_transcript_exon_variant	Exon 1 of 2
CLTA	ENST00000464497.5	n.*101+11353A>G		intron_variant	Intron 6 of 7	5		ENSP00000419158.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000805 AC: 2 AN: 248350 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460942 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726812

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111390

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000831 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sialuria;C1853926:GNE myopathy Benign:1

Jun 04, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Benign	2.8
DANN	Benign	0.89
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.2
REVEL	Benign	0.022
Sift4G	Uncertain	0.017	D
Vest4		0.43
MVP		0.74
ClinPred		0.065	T
GERP RS		2.3
PromoterAI		-0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs200763627; hg19: chr9-36276924;