6-31860510-C-G

Variant names:

• chr6-31860510-C-G
• NM_000434.4:c.727G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000434.4(NEU1):​c.727G>C​(p.Gly243Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEU1 NM_000434.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.18

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.994

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEU1	NM_000434.4	c.727G>C	p.Gly243Arg	missense_variant	Exon 4 of 6	ENST00000375631.5	NP_000425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEU1	ENST00000375631.5	c.727G>C	p.Gly243Arg	missense_variant	Exon 4 of 6	1	NM_000434.4	ENSP00000364782.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.97	D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.056	T
Polyphen		0.97	D
Vest4		0.99
MutPred		0.94		Loss of glycosylation at S244 (P = 0.0532);
MVP		0.99
MPC		1.5
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.58
gMVP		0.94

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31828287;