Variant 17-51161675-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000269.3(NME1):c.342-53C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,289,496 control chromosomes in the GnomAD database, including 24,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4318 hom., cov: 33)

Exomes 𝑓: 0.18 ( 20334 hom. )

Consequence

NME1
NM_000269.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.69

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:

NME1-NME2 (HGNC:):

NME1-NME2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-51161675-C-A is Benign according to our data. Variant chr17-51161675-C-A is described in ClinVar as [Benign]. Clinvar id is 2688180.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NME1	NM_000269.3 linkuse as main transcript	c.342-53C>A	intron_variant	ENST00000393196.8	NP_000260.1	P15531-1A0A384MTW7
NME1-NME2	NM_001018136.3 linkuse as main transcript	c.341+403C>A	intron_variant		NP_001018146.1	P22392-2
NME1	NM_198175.1 linkuse as main transcript	c.417-53C>A	intron_variant		NP_937818.1	P15531-2
NME1-NME2	NR_037149.2 linkuse as main transcript	n.669+403C>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NME1	ENST00000393196.8 linkuse as main transcript	c.342-53C>A		intron_variant		1	NM_000269.3	ENSP00000376892.3		P15531-1
NME1-NME2	ENST00000555572.1 linkuse as main transcript	c.416+403C>A		intron_variant		2		ENSP00000451932.1		Q32Q12

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34454

AN:

151992

Hom.:

4303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.221

GnomAD4 exome

AF:

0.183

AC:

208537

AN:

1137386

Hom.:

20334

Cov.:

AF XY:

0.181

AC XY:

104969

AN XY:

581220

show subpopulations

Gnomad4 AFR exome

AF:

0.337

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.195

GnomAD4 genome

AF:

0.227

AC:

34505

AN:

152110

Hom.:

4318

Cov.:

AF XY:

0.223

AC XY:

16585

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.335

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.194

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.219

Alfa

AF:

0.182

Hom.:

2643

Bravo

AF:

0.233

Asia WGS

AF:

0.207

AC:

718

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 39. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.27

DANN

Benign

0.74

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over