rs62001868

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

Clinical Significance

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

Conservation

PhyloP100: 0.316

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 links:

ENSG00000290149 (HGNC:):

ENSG00000290149 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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
NME8	NM_016616.5 link	c.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	UniProt
NME8	ENST00000199447.9 link	c.840A>G	p.Arg280Arg	synonymous_variant	Exon 12 of 18	1	NM_016616.5	ENSP00000199447.4	Q8N427
NME8	ENST00000440017.5 link	c.840A>G	p.Arg280Arg	synonymous_variant	Exon 11 of 16	1		ENSP00000397063.1	Q8N427
ENSG00000290149	ENST00000476620.1 link	c.-38+19508A>G		intron_variant	Intron 2 of 3	4		ENSP00000425858.1	D6RIH7
NME8	ENST00000426106.1 link	n.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.:

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

GnomAD3 exomes

AF:

0.122

AC:

30433

AN:

250106

Hom.:

2407

AF XY:

0.123

AC XY:

16567

AN XY:

135194

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 SAS exome

AF:

0.224

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.:

AF XY:

0.0965

AC XY:

70030

AN XY:

725802

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.0590

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.0727

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.138

AC:

21060

AN:

152098

Hom.:

1896

Cov.:

AF XY:

0.146

AC XY:

10854

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.241

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.0634

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.0723

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0992

Hom.:

589

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over