rs34214448

Positions:

• chr17-51154651-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NME1	NM_000269.3	c.-5+989G>T		intron_variant		ENST00000393196.8	NP_000260.1
NME1-NME2	NM_001018136.3	c.-5+989G>T		intron_variant			NP_001018146.1
NME1	NM_198175.1	c.71+207G>T		intron_variant			NP_937818.1
NME1-NME2	NR_037149.2	n.324+207G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NME1	ENST00000393196.8	c.-5+989G>T		intron_variant		1	NM_000269.3	ENSP00000376892.3
NME1-NME2	ENST00000555572.1	c.71+207G>T		intron_variant		2		ENSP00000451932.1

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

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.400

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 v4.3

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

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: rs34214448; hg19: chr17-49232012;