rs9286846

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPL	NM_030769.3	c.778+1317G>A		intron_variant		ENST00000367553.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPL	ENST00000367553.6	c.778+1317G>A		intron_variant		1	NM_030769.3	P1

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

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.0457

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0555

Gnomad4 FIN AF: 0.00227

Gnomad4 NFE AF: 0.00709

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0222 Hom.: 70

Bravo AF: 0.0880

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs9286846; hg19: chr1-182796272;