rs9286846

Variant names:

• chr1-182827137-G-A
• rs9286846
• NM_030769.3:c.778+1317G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-182827137-G-A
• chr1-182827137-G-T

Variant summary

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

The NM_030769.3(NPL):​c.778+1317G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,178 control chromosomes in the GnomAD database, including 1,287 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 0.078 (1287 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: NPL NM_030769.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 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.778+1317G>A		intron	N/A	NP_110396.1	Q9BXD5-1
	NPL	NM_001200050.2		c.721+1317G>A		intron	N/A	NP_001186979.1	Q9BXD5-2
	NPL	NM_001200056.2		c.778+1317G>A		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.778+1317G>A		intron	N/A	ENSP00000356524.1	Q9BXD5-1
	NPL	ENST00000258317.6	TSL:1	c.778+1317G>A		intron	N/A	ENSP00000258317.2	Q9BXD5-1
	NPL	ENST00000367554.7	TSL:1	c.721+1317G>A		intron	N/A	ENSP00000356525.3	Q9BXD5-2

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11901 AN: 152060 Hom.: 1279 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.00227

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.00710

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0784 AC: 11937 AN: 152178 Hom.: 1287 Cov.: 32 AF XY: 0.0770 AC XY: 5727 AN XY: 74406

African (AFR) AF: 0.245 AC: 10184 AN: 41486

American (AMR) AF: 0.0457 AC: 698 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3470

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5188

South Asian (SAS) AF: 0.0555 AC: 268 AN: 4828

European-Finnish (FIN) AF: 0.00227 AC: 24 AN: 10592

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.00709 AC: 482 AN: 68010

Other (OTH) AF: 0.0639 AC: 135 AN: 2112

Alfa AF: 0.0380 Hom.: 127

Bravo AF: 0.0880

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.86
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs9286846; hg19: chr1-182796272;