GeneBe

rs199901385

Variant names:

Variant summary

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

The NM_016616.5(NME8):​c.454C>A​(p.Gln152Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,428,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NME8
NM_016616.5 missense, splice_region

Scores

19
Splicing: ADA: 0.0002901
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.912
Variant links:
Genes affected
NME8 (HGNC:16473): (NME/NM23 family member 8) This gene encodes a protein with an N-terminal thioredoxin domain and three C-terminal nucleoside diphosphate kinase (NDK) domains, but the NDK domains are thought to be catalytically inactive. The sea urchin ortholog of this gene encodes a component of sperm outer dynein arms, and the protein is implicated in ciliary function. Mutations in this gene are implicated in primary ciliary dyskinesia type 6.[provided by RefSeq, Nov 2009]

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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=0.07597023).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NME8NM_016616.5 linkc.454C>A p.Gln152Lys missense_variant, splice_region_variant Exon 8 of 18 ENST00000199447.9 NP_057700.3 Q8N427

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NME8ENST00000199447.9 linkc.454C>A p.Gln152Lys missense_variant, splice_region_variant Exon 8 of 18 1 NM_016616.5 ENSP00000199447.4 Q8N427
ENSG00000290149ENST00000476620.1 linkc.-38+6117C>A intron_variant Intron 2 of 3 4 ENSP00000425858.1 D6RIH7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000210
AC:
3
AN:
1428996
Hom.:
0
Cov.:
25
AF XY:
0.00000140
AC XY:
1
AN XY:
712994
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
12
DANN
Benign
0.71
DEOGEN2
Benign
0.0021
T;T;.;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.35
.;T;T;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.076
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.;.;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.14
N;N;N;N
REVEL
Benign
0.050
Sift
Benign
0.88
T;T;T;T
Sift4G
Benign
0.81
T;T;T;T
Polyphen
0.015
B;.;.;B
Vest4
0.11
MutPred
0.33
Gain of ubiquitination at Q152 (P = 0.0101);.;.;Gain of ubiquitination at Q152 (P = 0.0101);
MVP
0.28
MPC
0.025
ClinPred
0.038
T
GERP RS
1.8
Varity_R
0.047
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00029
dbscSNV1_RF
Benign
0.080
SpliceAI score (max)
0.26
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.26
Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-37903064; API