rs968121109

Variant names:

• chr6-31859539-C-G
• rs968121109
• NM_000434.4:c.*180G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31859539-C-G
• chr6-31859539-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000434.4(NEU1):​c.*180G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 549,346 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: NEU1 NM_000434.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 0 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: Genomics England PanelApp, G2P, 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: 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 (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000434.4. 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
	NEU1	NM_000434.4	MANE Select	c.*180G>C		3_prime_UTR	Exon 6 of 6	NP_000425.1	Q5JQI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEU1	ENST00000375631.5	TSL:1 MANE Select	c.*180G>C		3_prime_UTR	Exon 6 of 6	ENSP00000364782.4	Q99519
	NEU1	ENST00000850553.1		c.*180G>C		3_prime_UTR	Exon 6 of 6	ENSP00000520846.1	A0ABB0MVI7
	NEU1	ENST00000877813.1		c.*180G>C		3_prime_UTR	Exon 6 of 6	ENSP00000547872.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000182 AC: 1 AN: 549346 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 294134

African (AFR) AF: 0.00 AC: 0 AN: 15488

American (AMR) AF: 0.00 AC: 0 AN: 32958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18588

East Asian (EAS) AF: 0.0000314 AC: 1 AN: 31876

South Asian (SAS) AF: 0.00 AC: 0 AN: 59246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 325808

Other (OTH) AF: 0.00 AC: 0 AN: 30104

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		0.15

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: rs968121109; hg19: chr6-31827316;