rs34214448

Variant names:

• chr17-51154651-G-T
• rs34214448
• NM_000269.3:c.-5+989G>T

Variant summary

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

The NM_000269.3(NME1):​c.-5+989G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,028 control chromosomes in the GnomAD database, including 11,330 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 0.39 (11330 hom., cov: 32)
• Consequence: NME1 NM_000269.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 16 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 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.-5+989G>T		intron	N/A	NP_000260.1	P15531-1
	NME1-NME2	NM_001018136.3		c.-5+989G>T		intron	N/A	NP_001018146.1
	NME1	NM_198175.1		c.71+207G>T		intron	N/A	NP_937818.1	P15531-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME1	ENST00000393196.8	TSL:1 MANE Select	c.-5+989G>T		intron	N/A	ENSP00000376892.3	P15531-1
	NME1-NME2	ENST00000393193.6	TSL:2	c.-5+989G>T		intron	N/A	ENSP00000376889.2
	NME1	ENST00000336097.7	TSL:1	c.71+207G>T		intron	N/A	ENSP00000337060.3	P15531-2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58684 AN: 151912 Hom.: 11316 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.386 AC: 58736 AN: 152028 Hom.: 11330 Cov.: 32 AF XY: 0.382 AC XY: 28406 AN XY: 74320

African (AFR) AF: 0.375 AC: 15552 AN: 41444

American (AMR) AF: 0.406 AC: 6201 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3466

East Asian (EAS) AF: 0.378 AC: 1959 AN: 5180

South Asian (SAS) AF: 0.307 AC: 1479 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3843 AN: 10568

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26953 AN: 67962

Other (OTH) AF: 0.400 AC: 845 AN: 2112

Alfa AF: 0.397 Hom.: 1436

Bravo AF: 0.391

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.6
DANN	Benign	0.25
PhyloP100		-0.0050
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34214448;

hg19: chr17-49232012;