1-182818662-G-A

Variant names:

• chr1-182818662-G-A
• rs58343016
• NM_030769.3:c.579G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_030769.3(NPL):​c.579G>A​(p.Gln193Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,614,188 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (69 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (55 hom.)
• Consequence: NPL NM_030769.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0350
• Publications: 1 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 1-182818662-G-A is Benign according to our data. Variant chr1-182818662-G-A is described in ClinVar as Benign. ClinVar VariationId is 780285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.035 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

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.579G>A	p.Gln193Gln	synonymous	Exon 9 of 13	NP_110396.1	Q9BXD5-1
	NPL	NM_001200050.2		c.522G>A	p.Gln174Gln	synonymous	Exon 7 of 11	NP_001186979.1	Q9BXD5-2
	NPL	NM_001200056.2		c.579G>A	p.Gln193Gln	synonymous	Exon 9 of 13	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.579G>A	p.Gln193Gln	synonymous	Exon 9 of 13	ENSP00000356524.1	Q9BXD5-1
	NPL	ENST00000258317.6	TSL:1	c.579G>A	p.Gln193Gln	synonymous	Exon 7 of 11	ENSP00000258317.2	Q9BXD5-1
	NPL	ENST00000367554.7	TSL:1	c.522G>A	p.Gln174Gln	synonymous	Exon 7 of 11	ENSP00000356525.3	Q9BXD5-2

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2321 AN: 152190 Hom.: 69 Cov.: 33

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00380 AC: 956 AN: 251432 AF XY: 0.00267

Gnomad AFR exome AF: 0.0523

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00152 AC: 2216 AN: 1461880 Hom.: 55 Cov.: 32 AF XY: 0.00132 AC XY: 962 AN XY: 727240

African (AFR) AF: 0.0565 AC: 1892 AN: 33480

American (AMR) AF: 0.00233 AC: 104 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1112008

Other (OTH) AF: 0.00285 AC: 172 AN: 60396

GnomAD4 genome AF: 0.0153 AC: 2325 AN: 152308 Hom.: 69 Cov.: 33 AF XY: 0.0145 AC XY: 1081 AN XY: 74484

African (AFR) AF: 0.0532 AC: 2211 AN: 41548

American (AMR) AF: 0.00555 AC: 85 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00762 Hom.: 15

Bravo AF: 0.0173

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.7
DANN	Benign	0.56
PhyloP100		0.035
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs58343016; hg19: chr1-182787797; COSMIC: COSV51124523; COSMIC: COSV51124523;