16-1770766-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_002513.3(NME3):​c.393G>A​(p.Lys131Lys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,449,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NME3
NM_002513.3 splice_region, synonymous

Scores

1
9
Splicing: ADA: 0.7044
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.91
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19542664).
BP6
Variant 16-1770766-C-T is Benign according to our data. Variant chr16-1770766-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3880077.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.91 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NME3NM_002513.3 linkc.393G>A p.Lys131Lys splice_region_variant, synonymous_variant Exon 5 of 5 ENST00000219302.8 NP_002504.2 Q13232
NME3XM_005255332.5 linkc.385G>A p.Glu129Lys missense_variant, splice_region_variant Exon 5 of 5 XP_005255389.1
NME3XM_011522504.3 linkc.404G>A p.Arg135Lys missense_variant, splice_region_variant Exon 5 of 5 XP_011520806.1
NME3XM_011522503.3 linkc.396G>A p.Arg132Arg splice_region_variant, synonymous_variant Exon 5 of 5 XP_011520805.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NME3ENST00000219302.8 linkc.393G>A p.Lys131Lys splice_region_variant, synonymous_variant Exon 5 of 5 1 NM_002513.3 ENSP00000219302.3 Q13232

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000882
AC:
2
AN:
226802
Hom.:
0
AF XY:
0.00000800
AC XY:
1
AN XY:
124962
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000116
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000621
AC:
9
AN:
1449830
Hom.:
0
Cov.:
31
AF XY:
0.00000555
AC XY:
4
AN XY:
720460
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000153
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000271
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 07, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
16
DANN
Benign
0.85
DEOGEN2
Benign
0.022
T
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.16
T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.20
T
Sift4G
Benign
0.32
T
MVP
0.93
GERP RS
2.5

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.70
dbscSNV1_RF
Benign
0.43
SpliceAI score (max)
0.010
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: rs1183704486; hg19: chr16-1820767; API