Genetic Variant NME1:c.-128C>T (chr17-51153539-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000269.3(NME1):c.-128C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,234 control chromosomes in the GnomAD database, including 3,804 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 0.22 ( 3803 hom., cov: 33)

Exomes 𝑓: 0.25 ( 1 hom. )

Consequence

NME1
NM_000269.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

Variant links:

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 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.06).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NME1	NM_000269.3 link	c.-128C>T	upstream_gene_variant	ENST00000393196.8	NP_000260.1	P15531-1A0A384MTW7
NME1-NME2	NM_001018136.3 link	c.-128C>T	upstream_gene_variant		NP_001018146.1	P22392-2
NME1	NM_198175.1 link	c.-273C>T	upstream_gene_variant		NP_937818.1	P15531-2
NME1-NME2	NR_037149.2 link	n.-20C>T	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME1	ENST00000393196.8 link	c.-128C>T		upstream_gene_variant		1	NM_000269.3	ENSP00000376892.3		P15531-1
NME1-NME2	ENST00000555572.1 link	c.-273C>T		upstream_gene_variant		2		ENSP00000451932.1		Q32Q12

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32684

AN:

152048

Hom.:

3792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.212

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.214

AC XY:

AN XY:

show subpopulations

Gnomad4 SAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.179

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.215

AC:

32722

AN:

152166

Hom.:

3803

Cov.:

AF XY:

0.212

AC XY:

15734

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.194

Gnomad4 NFE

AF:

0.183

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.181

Hom.:

3709

Bravo

AF:

0.220

Asia WGS

AF:

0.200

AC:

694

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over