rs2598044

Variant names:

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.177C>T(p.Asp59Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,605,020 control chromosomes in the GnomAD database, including 49,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6014 hom., cov: 33)

Exomes 𝑓: 0.24 ( 43970 hom. )

Consequence

NME8
NM_016616.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.953

Publications

16 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

NME8 links:

ENSG00000290149 (HGNC:):

ENSG00000290149 links:

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=-0.68).

BP6

Variant 7-37850714-C-T is Benign according to our data. Variant chr7-37850714-C-T is described in ClinVar as Benign. ClinVar VariationId is 164799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.953 with no splicing effect.

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.177C>T	p.Asp59Asp	synonymous_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.177C>T	p.Asp59Asp	synonymous_variant	Exon 5 of 18	1	NM_016616.5	ENSP00000199447.4		Q8N427
ENSG00000290149	ENST00000476620.1 link	c.-109-6560C>T		intron_variant	Intron 1 of 3	4		ENSP00000425858.1		D6RIH7

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41818

AN:

151936

Hom.:

6003

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:

0.245

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.257

GnomAD2 exomes

AF:

0.229

AC:

57476

AN:

250792

AF XY:

0.224

show subpopulations

Gnomad AFR exome

AF:

0.374

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.236

GnomAD4 exome

AF:

0.241

AC:

349803

AN:

1452966

Hom.:

43970

Cov.:

AF XY:

0.238

AC XY:

172214

AN XY:

723382

show subpopulations

African (AFR)

AF:

0.370

AC:

12305

AN:

33254

American (AMR)

AF:

0.207

AC:

9237

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

7330

AN:

26072

East Asian (EAS)

AF:

0.183

AC:

7242

AN:

39656

South Asian (SAS)

AF:

0.138

AC:

11855

AN:

86138

European-Finnish (FIN)

AF:

0.235

AC:

12549

AN:

53372

Middle Eastern (MID)

AF:

0.237

AC:

1323

AN:

5574

European-Non Finnish (NFE)

AF:

0.248

AC:

273417

AN:

1104120

Other (OTH)

AF:

0.242

AC:

14545

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

13304

26608

39911

53215

66519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9204

18408

27612

36816

46020

<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:

0.275

AC:

41860

AN:

152054

Hom.:

6014

Cov.:

AF XY:

0.272

AC XY:

20220

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.366

AC:

15162

AN:

41462

American (AMR)

AF:

0.250

AC:

3816

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

972

AN:

3468

East Asian (EAS)

AF:

0.180

AC:

934

AN:

5178

South Asian (SAS)

AF:

0.136

AC:

656

AN:

4818

European-Finnish (FIN)

AF:

0.245

AC:

2591

AN:

10556

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.250

AC:

16959

AN:

67970

Other (OTH)

AF:

0.256

AC:

541

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1549

3098

4647

6196

7745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<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:

0.256

Hom.:

4231

Bravo

AF:

0.277

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

Asp59Asp in exon 5 of TXNDC3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 36.8% (1622/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2598044). -

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

May 04, 2021

GeneDx

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

-0.68

CADD

Benign

1.0

(source)

DANN

Benign

0.73

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over