16-1770891-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002513.3(NME3):​c.382G>A​(p.Glu128Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,577,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

NME3
NM_002513.3 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04
Variant links:
Genes affected
NME3 (HGNC:7851): (NME/NM23 nucleoside diphosphate kinase 3) Predicted to enable nucleoside diphosphate kinase activity. Predicted to be involved in apoptotic process and nucleotide metabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NME3NM_002513.3 linkc.382G>A p.Glu128Lys missense_variant Exon 4 of 5 ENST00000219302.8 NP_002504.2 Q13232
NME3XM_005255332.5 linkc.382G>A p.Glu128Lys missense_variant, splice_region_variant Exon 4 of 5 XP_005255389.1
NME3XM_011522503.3 linkc.393G>A p.Ser131Ser splice_region_variant, synonymous_variant Exon 4 of 5 XP_011520805.1
NME3XM_011522504.3 linkc.393G>A p.Ser131Ser synonymous_variant Exon 4 of 5 XP_011520806.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NME3ENST00000219302.8 linkc.382G>A p.Glu128Lys missense_variant Exon 4 of 5 1 NM_002513.3 ENSP00000219302.3 Q13232

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152210
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000227
AC:
5
AN:
220072
Hom.:
0
AF XY:
0.0000166
AC XY:
2
AN XY:
120714
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000518
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000393
AC:
56
AN:
1425694
Hom.:
0
Cov.:
31
AF XY:
0.0000341
AC XY:
24
AN XY:
704004
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.0000238
Gnomad4 ASJ exome
AF:
0.0000410
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.0000170
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152210
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000604
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000118
AC:
1
ExAC
AF:
0.0000167
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.382G>A (p.E128K) alteration is located in exon 4 (coding exon 4) of the NME3 gene. This alteration results from a G to A substitution at nucleotide position 382, causing the glutamic acid (E) at amino acid position 128 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Benign
-0.083
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.35
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Uncertain
0.23
D
MetaRNN
Uncertain
0.72
D;D
MetaSVM
Uncertain
-0.0040
T
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-2.3
N;N
REVEL
Uncertain
0.37
Sift
Benign
0.065
T;T
Sift4G
Benign
0.065
T;T
Polyphen
0.99
D;.
Vest4
0.77
MVP
0.82
MPC
1.1
ClinPred
0.62
D
GERP RS
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.75
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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.

Other links and lift over

dbSNP: rs371192760; hg19: chr16-1820892; API