rs117681493

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016616.5(NME8):c.528+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,559,612 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 50 hom. )

Consequence

NME8
NM_016616.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.08

Publications

1 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 7-37864432-T-C is Benign according to our data. Variant chr7-37864432-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5 link	c.528+11T>C		intron_variant	Intron 9 of 17	ENST00000199447.9	NP_057700.3	Q8N427

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9 link	c.528+11T>C		intron_variant	Intron 9 of 17	1	NM_016616.5	ENSP00000199447.4		Q8N427
ENSG00000290149	ENST00000476620.1 link	c.-38+7087T>C		intron_variant	Intron 2 of 3	4		ENSP00000425858.1		D6RIH7

Frequencies

GnomAD3 genomes

AF:

0.00448

AC:

674

AN:

150392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00114

Gnomad AMI

AF:

0.0145

Gnomad AMR

AF:

0.00180

Gnomad ASJ

AF:

0.00493

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00151

Gnomad FIN

AF:

0.00536

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00743

Gnomad OTH

AF:

0.00295

GnomAD2 exomes

AF:

0.00480

AC:

1101

AN:

229224

AF XY:

0.00509

show subpopulations

Gnomad AFR exome

AF:

0.000812

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00423

Gnomad NFE exome

AF:

0.00829

Gnomad OTH exome

AF:

0.00267

GnomAD4 exome

AF:

0.00669

AC:

9421

AN:

1409104

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

4527

AN XY:

700538

show subpopulations

African (AFR)

AF:

0.000742

AC:

AN:

32366

American (AMR)

AF:

0.00121

AC:

AN:

42906

Ashkenazi Jewish (ASJ)

AF:

0.00336

AC:

AN:

25006

East Asian (EAS)

AF:

0.00

AC:

AN:

38552

South Asian (SAS)

AF:

0.00271

AC:

227

AN:

83830

European-Finnish (FIN)

AF:

0.00488

AC:

251

AN:

51412

Middle Eastern (MID)

AF:

0.000551

AC:

AN:

5444

European-Non Finnish (NFE)

AF:

0.00794

AC:

8512

AN:

1071612

Other (OTH)

AF:

0.00462

AC:

268

AN:

57976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

430

860

1290

1720

2150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.00448

AC:

674

AN:

150508

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

304

AN XY:

73362

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

41246

American (AMR)

AF:

0.00180

AC:

AN:

15000

Ashkenazi Jewish (ASJ)

AF:

0.00493

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00151

AC:

AN:

4622

European-Finnish (FIN)

AF:

0.00536

AC:

AN:

10266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00743

AC:

502

AN:

67542

Other (OTH)

AF:

0.00292

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00519

Hom.:

Bravo

AF:

0.00442

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

528+11T>C in intron 9 of TXNDC3: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence. It has been identified in 0.8% (66/8520) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs117681493). -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 6

Benign:1

Jan 28, 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

-0.48

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.1

Mutation Taster

=99/1

polymorphism

(source)

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

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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