rs41276027

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.1479A>T(p.Ile493Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,606,362 control chromosomes in the GnomAD database, including 88,552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6052 hom., cov: 32)

Exomes 𝑓: 0.33 ( 82500 hom. )

Consequence

NME8
NM_016616.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.337

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=-0.97).

BP6

Variant 7-37894545-A-T is Benign according to our data. Variant chr7-37894545-A-T is described in ClinVar as [Benign]. Clinvar id is 164805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-37894545-A-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.337 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5 link	c.1479A>T	p.Ile493Ile	synonymous_variant	Exon 16 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.1479A>T	p.Ile493Ile	synonymous_variant	Exon 16 of 18	1	NM_016616.5	ENSP00000199447.4	Q8N427
NME8	ENST00000440017.5 link	c.1479A>T	p.Ile493Ile	synonymous_variant	Exon 15 of 16	1		ENSP00000397063.1	Q8N427
ENSG00000290149	ENST00000476620.1 link	c.-38+37200A>T		intron_variant	Intron 2 of 3	4		ENSP00000425858.1	D6RIH7

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38047

AN:

151874

Hom.:

6051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0676

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.276

GnomAD3 exomes

AF:

0.273

AC:

68343

AN:

250598

Hom.:

10693

AF XY:

0.273

AC XY:

37013

AN XY:

135518

show subpopulations

Gnomad AFR exome

AF:

0.0591

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.128

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.327

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.328

AC:

476342

AN:

1454370

Hom.:

82500

Cov.:

AF XY:

0.324

AC XY:

234386

AN XY:

723898

show subpopulations

Gnomad4 AFR exome

AF:

0.0524

Gnomad4 AMR exome

AF:

0.242

Gnomad4 ASJ exome

AF:

0.300

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.333

Gnomad4 NFE exome

AF:

0.359

Gnomad4 OTH exome

AF:

0.312

GnomAD4 genome

AF:

0.250

AC:

38037

AN:

151992

Hom.:

6052

Cov.:

AF XY:

0.246

AC XY:

18266

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0674

Gnomad4 AMR

AF:

0.247

Gnomad4 ASJ

AF:

0.306

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.322

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.328

Hom.:

2807

Bravo

AF:

0.240

Asia WGS

AF:

0.152

AC:

528

AN:

3474

EpiCase

AF:

0.350

EpiControl

AF:

0.343

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

Ile493Ile in exon 16 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 0.5% (47/8598) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs41276027). -

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

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.41

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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