17-51153539-C-T

Variant names:

• chr17-51153539-C-T
• rs2302254
• ENST00000911793.1:c.-128C>T

Variant summary

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

The ENST00000911793.1(NME1):​c.-128C>T variant causes a 5 prime UTR 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 ENST00000911793.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 31 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000911793.1. 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.-128C>T		upstream_gene	N/A	NP_000260.1	P15531-1
	NME1-NME2	NM_001018136.3		c.-128C>T		upstream_gene	N/A	NP_001018146.1
	NME1	NM_198175.1		c.-273C>T		upstream_gene	N/A	NP_937818.1	P15531-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME1	ENST00000911793.1		c.-128C>T		5_prime_UTR	Exon 1 of 5	ENSP00000581852.1
	NME1	ENST00000911790.1		c.-5+499C>T		intron	N/A	ENSP00000581849.1
	NME1	ENST00000393196.8	TSL:1 MANE Select	c.-128C>T		upstream_gene	N/A	ENSP00000376892.3	P15531-1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32684 AN: 152048 Hom.: 3792 Cov.: 33

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: 17 AN: 68 Hom.: 1 Cov.: 0 AF XY: 0.214 AC XY: 9 AN XY: 42

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.344 AC: 11 AN: 32

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.179 AC: 5 AN: 28

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.215 AC: 32722 AN: 152166 Hom.: 3803 Cov.: 33 AF XY: 0.212 AC XY: 15734 AN XY: 74376

African (AFR) AF: 0.295 AC: 12245 AN: 41514

American (AMR) AF: 0.201 AC: 3066 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1236 AN: 5170

South Asian (SAS) AF: 0.117 AC: 565 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2049 AN: 10586

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12477 AN: 68002

Other (OTH) AF: 0.211 AC: 445 AN: 2114

Alfa AF: 0.192 Hom.: 9610

Bravo AF: 0.220

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		-0.049
PromoterAI		-0.019	Neutral
Mutation Taster		=300/0	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: rs2302254; hg19: chr17-49230900;