rs62001870

Positions:

chr7-37884321-T-C

Variant summary

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

The NM_016616.5(NME8):c.1013T>C(p.Ile338Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0493 in 1,588,014 control chromosomes in the GnomAD database, including 2,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 135 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2077 hom. )

Consequence

NME8
NM_016616.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.49

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035468638).

BP6

Variant 7-37884321-T-C is Benign according to our data. Variant chr7-37884321-T-C is described in ClinVar as [Benign]. Clinvar id is 164803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NME8	NM_016616.5 linkuse as main transcript	c.1013T>C	p.Ile338Thr	missense_variant	13/18	ENST00000199447.9	NP_057700.3	Q8N427

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NME8	ENST00000199447.9 linkuse as main transcript	c.1013T>C	p.Ile338Thr	missense_variant	13/18	1	NM_016616.5	ENSP00000199447.4	Q8N427
NME8	ENST00000440017.5 linkuse as main transcript	c.1013T>C	p.Ile338Thr	missense_variant	12/16	1		ENSP00000397063.1	Q8N427
ENSG00000290149	ENST00000476620.1 linkuse as main transcript	c.-38+26976T>C		intron_variant		4		ENSP00000425858.1	D6RIH7
NME8	ENST00000426106.1 linkuse as main transcript	n.124T>C		non_coding_transcript_exon_variant	3/5	5		ENSP00000408841.1	F8WEA2

Frequencies

GnomAD3 genomes

AF:

0.0360

AC:

5478

AN:

152134

Hom.:

135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0254

Gnomad ASJ

AF:

0.0649

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0320

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0565

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0400

AC:

10028

AN:

250634

Hom.:

262

AF XY:

0.0415

AC XY:

5616

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.00938

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.0703

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0314

Gnomad FIN exome

AF:

0.0348

Gnomad NFE exome

AF:

0.0575

Gnomad OTH exome

AF:

0.0452

GnomAD4 exome

AF:

0.0508

AC:

72892

AN:

1435762

Hom.:

2077

Cov.:

AF XY:

0.0508

AC XY:

36343

AN XY:

716000

show subpopulations

Gnomad4 AFR exome

AF:

0.00764

Gnomad4 AMR exome

AF:

0.0202

Gnomad4 ASJ exome

AF:

0.0662

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0319

Gnomad4 FIN exome

AF:

0.0346

Gnomad4 NFE exome

AF:

0.0572

Gnomad4 OTH exome

AF:

0.0466

GnomAD4 genome

AF:

0.0359

AC:

5473

AN:

152252

Hom.:

135

Cov.:

AF XY:

0.0337

AC XY:

2506

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.0649

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.0320

Gnomad4 NFE

AF:

0.0565

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0521

Hom.:

341

Bravo

AF:

0.0333

TwinsUK

AF:

0.0558

AC:

207

ALSPAC

AF:

0.0623

AC:

240

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.0528

AC:

454

ExAC

AF:

0.0394

AC:

4783

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0558

EpiControl

AF:

0.0563

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ile338Thr in exon 13 of TXNDC3: This variant is not expected to have clinical si gnificance because it has been identified in 5.3% (454/8594) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs62001870). -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2014

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Primary ciliary dyskinesia 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

.;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Pathogenic

3.3

M;M

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.72

MPC

0.18

ClinPred

0.064

GERP RS

4.0

Varity_R

0.80

gMVP

0.76

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