rs9267649

Variant names:

• chr6-31857051-A-G
• rs9267649
• ENST00000850553.1:c.*2668T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000850553.1(NEU1):​c.*2668T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,110 control chromosomes in the GnomAD database, including 58,882 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (58882 hom., cov: 31)
• Consequence: NEU1 ENST00000850553.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 38 publications found

Genes affected

NEU1 (HGNC:7758): (neuraminidase 1) The protein encoded by this gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis, a lysosomal storage disease that can be type 1 (cherry red spot-myoclonus syndrome or normosomatic type), which is late-onset, or type 2 (the dysmorphic type), which occurs at an earlier age with increased severity. [provided by RefSeq, Jul 2008]

NEU1 Gene-Disease associations (from GenCC):

• sialidosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• sialidosis type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital sialidosis type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• juvenile sialidosis type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sialidosis type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEU1	ENST00000850553.1	c.*2668T>C		downstream_gene_variant				ENSP00000520846.1

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133360 AN: 151992 Hom.: 58818 Cov.: 31

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.905

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.878 AC: 133484 AN: 152110 Hom.: 58882 Cov.: 31 AF XY: 0.878 AC XY: 65264 AN XY: 74366

African (AFR) AF: 0.966 AC: 40112 AN: 41518

American (AMR) AF: 0.914 AC: 13959 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3240 AN: 3468

East Asian (EAS) AF: 0.804 AC: 4158 AN: 5172

South Asian (SAS) AF: 0.882 AC: 4255 AN: 4822

European-Finnish (FIN) AF: 0.844 AC: 8912 AN: 10562

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55951 AN: 67976

Other (OTH) AF: 0.905 AC: 1914 AN: 2114

Alfa AF: 0.846 Hom.: 220521

Bravo AF: 0.887

Asia WGS AF: 0.895 AC: 3116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.36
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs9267649; hg19: chr6-31824828;