rs141307270

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.388-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,557,942 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

NME8
NM_016616.5 splice_region, intron

Scores

Splicing: ADA: 0.00004923

Clinical Significance

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

Conservation

PhyloP100: -0.793

Publications

0 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=-0.81).

BP6

Variant 7-37863393-T-C is Benign according to our data. Variant chr7-37863393-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 260761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016616.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	NM_016616.5	MANE Select	c.388-3T>C		splice_region intron	N/A	NP_057700.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NME8	ENST00000199447.9	TSL:1 MANE Select	c.388-3T>C	splice_region intron	N/A	ENSP00000199447.4
NME8	ENST00000440017.5	TSL:1	c.388-3T>C	splice_region intron	N/A	ENSP00000397063.1
ENSG00000290149	ENST00000476620.1	TSL:4	c.-38+6048T>C	intron	N/A	ENSP00000425858.1

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

285

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000527

AC:

132

AN:

250700

AF XY:

0.000391

show subpopulations

Gnomad AFR exome

AF:

0.00746

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000199

AC:

280

AN:

1405606

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

116

AN XY:

702808

show subpopulations

African (AFR)

AF:

0.00673

AC:

218

AN:

32380

American (AMR)

AF:

0.000403

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25790

East Asian (EAS)

AF:

0.00

AC:

AN:

39380

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53210

Middle Eastern (MID)

AF:

0.000708

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1061120

Other (OTH)

AF:

0.000308

AC:

AN:

58482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.00186

AC:

284

AN:

152336

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00654

AC:

272

AN:

41582

American (AMR)

AF:

0.000523

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000999

Hom.:

Bravo

AF:

0.00226

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia

Benign:1

Aug 07, 2015

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely 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.

Primary ciliary dyskinesia 6

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.16

(source)

DANN

Benign

0.70

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.044

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over