rs3213975

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.1603T>C(p.Leu535Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,613,196 control chromosomes in the GnomAD database, including 44,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 3886 hom., cov: 31)

Exomes 𝑓: 0.23 ( 40147 hom. )

Consequence

NME8
NM_016616.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.314

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-37896928-T-C is Benign according to our data. Variant chr7-37896928-T-C is described in ClinVar as [Benign]. Clinvar id is 164806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.314 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5 link	c.1603T>C	p.Leu535Leu	synonymous_variant	Exon 17 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.1603T>C	p.Leu535Leu	synonymous_variant	Exon 17 of 18	1	NM_016616.5	ENSP00000199447.4	Q8N427
NME8	ENST00000440017.5 link	c.1603T>C	p.Leu535Leu	synonymous_variant	Exon 16 of 16	1		ENSP00000397063.1	Q8N427
ENSG00000290149	ENST00000476620.1 link	c.-38+39583T>C		intron_variant	Intron 2 of 3	4		ENSP00000425858.1	D6RIH7
NME8	ENST00000476435.1 link	n.112T>C		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34381

AN:

151760

Hom.:

3883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.220

GnomAD3 exomes

AF:

0.242

AC:

60776

AN:

251196

Hom.:

7563

AF XY:

0.244

AC XY:

33121

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.267

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.233

AC:

340358

AN:

1461318

Hom.:

40147

Cov.:

AF XY:

0.233

AC XY:

169736

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.242

Gnomad4 NFE exome

AF:

0.232

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.227

AC:

34408

AN:

151878

Hom.:

3886

Cov.:

AF XY:

0.227

AC XY:

16847

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.266

Gnomad4 EAS

AF:

0.221

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.244

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.238

Hom.:

5868

Bravo

AF:

0.229

Asia WGS

AF:

0.229

AC:

796

AN:

3478

EpiCase

AF:

0.239

EpiControl

AF:

0.245

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

Leu535Leu in exon 17 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 24.2% (2077/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs3213975). -

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

Nov 12, 2018

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

-0.84

CADD

Benign

0.45

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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