NPL p.Gln193Gln

Variant names:

• chr1-182818659-A-A
• ENST00000367553.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-182818660--
• chr1-182818662-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030769.3(NPL):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NPL NM_030769.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 0 publications found

Genes affected

NPL (HGNC:16781): (N-acetylneuraminate pyruvate lyase) This gene encodes a member of the N-acetylneuraminate lyase sub-family of (beta/alpha)(8)-barrel enzymes. N-acetylneuraminate lyases regulate cellular concentrations of N-acetyl-neuraminic acid (sialic acid) by mediating the reversible conversion of sialic acid into N-acetylmannosamine and pyruvate. A pseudogene of this gene is located on the short arm of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030769.3. 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
	NPL	NM_030769.3	MANE Select	c.		intron	N/A	NP_110396.1	Q9BXD5-1
	NPL	NM_001200050.2		c.		intron	N/A	NP_001186979.1	Q9BXD5-2
	NPL	NM_001200056.2		c.		intron	N/A	NP_001186985.1	Q9BXD5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPL	ENST00000367553.6	TSL:1 MANE Select	c.		exon_region	Exon 9 of 13	ENSP00000356524.1	Q9BXD5-1
	NPL	ENST00000258317.6	TSL:1	c.		exon_region	Exon 7 of 11	ENSP00000258317.2	Q9BXD5-1
	NPL	ENST00000367554.7	TSL:1	c.		exon_region	Exon 7 of 11	ENSP00000356525.3	Q9BXD5-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-182787794;