rs2318785

Positions:

• chr17-51162157-G-A
• chr17-51162157-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000269.3(NME1):​c.*312G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 273,776 control chromosomes in the GnomAD database, including 29,731 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 0.47 (16633 hom., cov: 31)
  • Exomes 𝑓: 0.46 (13098 hom.)
• Consequence: NME1 NM_000269.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25

Genes affected

NME1 (HGNC:7849): (NME/NM23 nucleoside diphosphate kinase 1) This gene (NME1) was identified because of its reduced mRNA transcript levels in highly metastatic cells. Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by this gene) and 'B' (encoded by NME2) isoforms. Mutations in this gene have been identified in aggressive neuroblastomas. Two transcript variants encoding different isoforms have been found for this gene. Co-transcription of this gene and the neighboring downstream gene (NME2) generates naturally-occurring transcripts (NME1-NME2), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Jul 2008]

NME1-NME2 (HGNC:33531): (NME1-NME2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NME1 and NME2 genes. The significance of this read-through transcription and the function of the resulting protein product have not yet been determined. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2010]

NME1-NME2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NME1	NM_000269.3	c.*312G>A		3_prime_UTR_variant	5/5	ENST00000393196.8	NP_000260.1
NME1-NME2	NM_001018136.3	c.341+885G>A		intron_variant			NP_001018146.1
NME1-NME2	NR_037149.2	n.669+885G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NME1	ENST00000393196.8	c.*312G>A		3_prime_UTR_variant	5/5	1	NM_000269.3	ENSP00000376892.3
NME1-NME2	ENST00000555572.1	c.416+885G>A		intron_variant		2		ENSP00000451932.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70786 AN: 151696 Hom.: 16626 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.456 AC: 55670 AN: 121962 Hom.: 13098 Cov.: 0 AF XY: 0.467 AC XY: 30448 AN XY: 65188

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.559

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.467 AC: 70827 AN: 151814 Hom.: 16633 Cov.: 31 AF XY: 0.471 AC XY: 34920 AN XY: 74184

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.483

Alfa AF: 0.431 Hom.: 12813

Bravo AF: 0.463

Asia WGS AF: 0.566 AC: 1971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.43

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: rs2318785; hg19: chr17-49239518;