3-48296786-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001308426.2(NME6):​c.134G>A​(p.Arg45Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,613,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

NME6
NM_001308426.2 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81
Variant links:
Genes affected
NME6 (HGNC:20567): (NME/NM23 nucleoside diphosphate kinase 6) Nucleoside diphosphate (NDP) kinases (EC 2.7.4.6), such as NME6, are ubiquitous enzymes that catalyze transfer of gamma-phosphates, via a phosphohistidine intermediate, between nucleoside and dioxynucleoside tri- and diphosphates (Mehus et al., 1999 [PubMed 10453732]).[supplied by OMIM, Jul 2010]
ZNF589 (HGNC:16747): (zinc finger protein 589) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. [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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12663242).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NME6NM_001308426.2 linkc.134G>A p.Arg45Gln missense_variant Exon 3 of 6 ENST00000442597.6 NP_001295355.1 O75414-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NME6ENST00000442597.6 linkc.134G>A p.Arg45Gln missense_variant Exon 3 of 6 1 NM_001308426.2 ENSP00000406642.1 O75414-1

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152076
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000459
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000597
AC:
15
AN:
251230
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000458
AC:
67
AN:
1461562
Hom.:
0
Cov.:
30
AF XY:
0.0000385
AC XY:
28
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.000657
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152076
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.000459
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000178
Hom.:
0
Bravo
AF:
0.000212
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.158G>A (p.R53Q) alteration is located in exon 3 (coding exon 3) of the NME6 gene. This alteration results from a G to A substitution at nucleotide position 158, causing the arginine (R) at amino acid position 53 to be replaced by a glutamine (Q). 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
Benign
0.11
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.051
.;.;T;T;T;.;T;T;.;.;.;T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.95
.;D;.;D;.;D;.;.;D;D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.13
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.1
L;.;L;L;L;L;L;L;L;.;.;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.4
N;N;.;N;N;D;N;N;N;N;D;D
REVEL
Benign
0.27
Sift
Uncertain
0.0070
D;T;.;T;T;D;T;T;D;T;T;D
Sift4G
Benign
0.22
T;T;.;T;T;D;T;T;T;T;.;.
Polyphen
1.0
D;.;B;B;B;D;B;B;D;B;.;.
Vest4
0.37
MVP
0.51
MPC
0.78
ClinPred
0.12
T
GERP RS
3.6
Varity_R
0.22
gMVP
0.82

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: rs368361118; hg19: chr3-48338276; API