rs2318785

Variant names:

• chr17-51162157-G-A
• rs2318785
• NM_000269.3:c.*312G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000269.3. 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
	NME1	NM_000269.3	MANE Select	c.*312G>A		3_prime_UTR	Exon 5 of 5	NP_000260.1	P15531-1
	NME1-NME2	NM_001018136.3		c.341+885G>A		intron	N/A	NP_001018146.1
	NME1-NME2	NR_037149.2		n.669+885G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME1	ENST00000393196.8	TSL:1 MANE Select	c.*312G>A		3_prime_UTR	Exon 5 of 5	ENSP00000376892.3	P15531-1
	NME1-NME2	ENST00000393193.6	TSL:2	c.341+885G>A		intron	N/A	ENSP00000376889.2
	NME1	ENST00000511355.5	TSL:5	c.*1039G>A		3_prime_UTR	Exon 4 of 4	ENSP00000428553.1	E5RHP0

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

African (AFR) AF: 0.501 AC: 1960 AN: 3910

American (AMR) AF: 0.372 AC: 2158 AN: 5796

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1621 AN: 3120

East Asian (EAS) AF: 0.587 AC: 3668 AN: 6252

South Asian (SAS) AF: 0.559 AC: 10379 AN: 18562

European-Finnish (FIN) AF: 0.431 AC: 2265 AN: 5252

Middle Eastern (MID) AF: 0.540 AC: 228 AN: 422

European-Non Finnish (NFE) AF: 0.422 AC: 30502 AN: 72280

Other (OTH) AF: 0.454 AC: 2889 AN: 6368

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

African (AFR) AF: 0.505 AC: 20915 AN: 41386

American (AMR) AF: 0.426 AC: 6489 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1759 AN: 3464

East Asian (EAS) AF: 0.590 AC: 3041 AN: 5152

South Asian (SAS) AF: 0.588 AC: 2833 AN: 4816

European-Finnish (FIN) AF: 0.453 AC: 4763 AN: 10514

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29478 AN: 67942

Other (OTH) AF: 0.483 AC: 1016 AN: 2102

Alfa AF: 0.444 Hom.: 20489

Bravo AF: 0.463

Asia WGS AF: 0.566 AC: 1971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.43
PhyloP100		-3.3
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: rs2318785; hg19: chr17-49239518;