rs62001868

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016616.5(NME8):​c.840A>G​(p.Arg280Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 1,610,984 control chromosomes in the GnomAD database, including 10,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1896 hom., cov: 32)
Exomes 𝑓: 0.093 ( 8469 hom. )

Consequence

NME8
NM_016616.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.316

Publications

11 publications found
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]
NME8 Gene-Disease associations (from GenCC):
  • primary ciliary dyskinesia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • primary ciliary dyskinesia 6
    Inheritance: AR Classification: LIMITED Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 7-37876853-A-G is Benign according to our data. Variant chr7-37876853-A-G is described in ClinVar as [Benign]. Clinvar id is 164802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.316 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NME8NM_016616.5 linkc.840A>G p.Arg280Arg synonymous_variant Exon 12 of 18 ENST00000199447.9 NP_057700.3 Q8N427

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NME8ENST00000199447.9 linkc.840A>G p.Arg280Arg synonymous_variant Exon 12 of 18 1 NM_016616.5 ENSP00000199447.4 Q8N427
NME8ENST00000440017.5 linkc.840A>G p.Arg280Arg synonymous_variant Exon 11 of 16 1 ENSP00000397063.1 Q8N427
ENSG00000290149ENST00000476620.1 linkc.-38+19508A>G intron_variant Intron 2 of 3 4 ENSP00000425858.1 D6RIH7
NME8ENST00000426106.1 linkn.106-7450A>G intron_variant Intron 2 of 4 5 ENSP00000408841.1 F8WEA2

Frequencies

GnomAD3 genomes
AF:
0.138
AC:
21038
AN:
151980
Hom.:
1887
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.241
Gnomad AMI
AF:
0.0461
Gnomad AMR
AF:
0.133
Gnomad ASJ
AF:
0.0634
Gnomad EAS
AF:
0.203
Gnomad SAS
AF:
0.227
Gnomad FIN
AF:
0.139
Gnomad MID
AF:
0.101
Gnomad NFE
AF:
0.0723
Gnomad OTH
AF:
0.104
GnomAD2 exomes
AF:
0.122
AC:
30433
AN:
250106
AF XY:
0.123
show subpopulations
Gnomad AFR exome
AF:
0.238
Gnomad AMR exome
AF:
0.112
Gnomad ASJ exome
AF:
0.0615
Gnomad EAS exome
AF:
0.198
Gnomad FIN exome
AF:
0.127
Gnomad NFE exome
AF:
0.0735
Gnomad OTH exome
AF:
0.101
GnomAD4 exome
AF:
0.0933
AC:
136071
AN:
1458886
Hom.:
8469
Cov.:
30
AF XY:
0.0965
AC XY:
70030
AN XY:
725802
show subpopulations
African (AFR)
AF:
0.250
AC:
8351
AN:
33364
American (AMR)
AF:
0.112
AC:
4988
AN:
44632
Ashkenazi Jewish (ASJ)
AF:
0.0590
AC:
1539
AN:
26102
East Asian (EAS)
AF:
0.200
AC:
7902
AN:
39446
South Asian (SAS)
AF:
0.223
AC:
19192
AN:
85934
European-Finnish (FIN)
AF:
0.125
AC:
6644
AN:
53354
Middle Eastern (MID)
AF:
0.0929
AC:
534
AN:
5746
European-Non Finnish (NFE)
AF:
0.0727
AC:
80739
AN:
1110044
Other (OTH)
AF:
0.103
AC:
6182
AN:
60264
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.462
Heterozygous variant carriers
0
5391
10782
16173
21564
26955
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
3296
6592
9888
13184
16480
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.138
AC:
21060
AN:
152098
Hom.:
1896
Cov.:
32
AF XY:
0.146
AC XY:
10854
AN XY:
74354
show subpopulations
African (AFR)
AF:
0.241
AC:
9997
AN:
41440
American (AMR)
AF:
0.133
AC:
2026
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.0634
AC:
220
AN:
3470
East Asian (EAS)
AF:
0.203
AC:
1051
AN:
5172
South Asian (SAS)
AF:
0.226
AC:
1091
AN:
4824
European-Finnish (FIN)
AF:
0.139
AC:
1471
AN:
10586
Middle Eastern (MID)
AF:
0.0884
AC:
26
AN:
294
European-Non Finnish (NFE)
AF:
0.0723
AC:
4918
AN:
67996
Other (OTH)
AF:
0.103
AC:
218
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
883
1765
2648
3530
4413
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
234
468
702
936
1170
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.105
Hom.:
863
Bravo
AF:
0.137
Asia WGS
AF:
0.205
AC:
713
AN:
3474
EpiCase
AF:
0.0701
EpiControl
AF:
0.0676

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 21, 2013
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Arg280Arg in exon 12 of TXNDC3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 22.9% (1011/4406) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs62001868). -

Primary ciliary dyskinesia Benign:1
Dec 01, 2014
Ambry Genetics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as 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. -

not provided Benign:1
May 04, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Primary ciliary dyskinesia 6 Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
2.5
DANN
Benign
0.81
PhyloP100
0.32
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs62001868; hg19: chr7-37916455; COSMIC: COSV107213999; API