rs2722372

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016616.5(NME8):c.128G>A(p.Arg43Lys) variant causes a missense change. The variant allele was found at a frequency of 0.244 in 1,607,830 control chromosomes in the GnomAD database, including 50,097 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6015 hom., cov: 33)

Exomes 𝑓: 0.24 ( 44082 hom. )

Consequence

NME8
NM_016616.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.05

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029492974).

BP6

Variant 7-37850665-G-A is Benign according to our data. Variant chr7-37850665-G-A is described in ClinVar as [Benign]. Clinvar id is 164798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-37850665-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5 link	c.128G>A	p.Arg43Lys	missense_variant	Exon 5 of 18	ENST00000199447.9	NP_057700.3	Q8N427

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9 link	c.128G>A	p.Arg43Lys	missense_variant	Exon 5 of 18	1	NM_016616.5	ENSP00000199447.4		Q8N427
ENSG00000290149	ENST00000476620.1 link	c.-109-6609G>A		intron_variant	Intron 1 of 3	4		ENSP00000425858.1		D6RIH7

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41829

AN:

152060

Hom.:

6004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.257

GnomAD3 exomes

AF:

0.229

AC:

57551

AN:

251018

Hom.:

7116

AF XY:

0.224

AC XY:

30376

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.375

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.236

GnomAD4 exome

AF:

0.241

AC:

351025

AN:

1455654

Hom.:

44082

Cov.:

AF XY:

0.238

AC XY:

172701

AN XY:

724522

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.207

Gnomad4 ASJ exome

AF:

0.281

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.248

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.275

AC:

41870

AN:

152176

Hom.:

6015

Cov.:

AF XY:

0.272

AC XY:

20226

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.249

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.252

Hom.:

6607

Bravo

AF:

0.277

TwinsUK

AF:

0.257

AC:

954

ALSPAC

AF:

0.255

AC:

983

ESP6500AA

AF:

0.369

AC:

1624

ESP6500EA

AF:

0.243

AC:

2090

ExAC

AF:

0.230

AC:

27946

Asia WGS

AF:

0.164

AC:

571

AN:

3478

EpiCase

AF:

0.246

EpiControl

AF:

0.246

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

Arg43Lys in exon 5 of TXNDC3: This variant is not expected to have clinical sign ificance because it has been identified in 36.9% (1624/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs2722372). -

Primary ciliary dyskinesia 6

Benign:2

May 18, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Dec 10, 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

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0024

T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.16

.;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.3

N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.13

MPC

0.021

ClinPred

0.0072

GERP RS

3.9

Varity_R

0.091

gMVP

0.28

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