Genetic Variant NME8:c.455-46C>T (chr7-37864302-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_016616.5(NME8):c.455-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,555,418 control chromosomes in the GnomAD database, including 424,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45451 hom., cov: 33)

Exomes 𝑓: 0.73 ( 378968 hom. )

Consequence

NME8
NM_016616.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.581

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 7-37864302-C-T is Benign according to our data. Variant chr7-37864302-C-T is described in ClinVar as [Benign]. Clinvar id is 260762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5 link	c.455-46C>T		intron_variant	Intron 8 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.455-46C>T		intron_variant	Intron 8 of 17	1	NM_016616.5	ENSP00000199447.4		Q8N427
ENSG00000290149	ENST00000476620.1 link	c.-38+6957C>T		intron_variant	Intron 2 of 3	4		ENSP00000425858.1		D6RIH7

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

117044

AN:

152062

Hom.:

45402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.876

Gnomad AMI

AF:

0.818

Gnomad AMR

AF:

0.722

Gnomad ASJ

AF:

0.773

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.705

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.770

GnomAD3 exomes

AF:

0.726

AC:

152607

AN:

210182

Hom.:

55806

AF XY:

0.727

AC XY:

82462

AN XY:

113480

show subpopulations

Gnomad AFR exome

AF:

0.879

Gnomad AMR exome

AF:

0.668

Gnomad ASJ exome

AF:

0.773

Gnomad EAS exome

AF:

0.563

Gnomad SAS exome

AF:

0.735

Gnomad FIN exome

AF:

0.717

Gnomad NFE exome

AF:

0.747

Gnomad OTH exome

AF:

0.741

GnomAD4 exome

AF:

0.733

AC:

1029169

AN:

1403236

Hom.:

378968

Cov.:

AF XY:

0.733

AC XY:

509729

AN XY:

694946

show subpopulations

Gnomad4 AFR exome

AF:

0.882

Gnomad4 AMR exome

AF:

0.678

Gnomad4 ASJ exome

AF:

0.776

Gnomad4 EAS exome

AF:

0.569

Gnomad4 SAS exome

AF:

0.737

Gnomad4 FIN exome

AF:

0.720

Gnomad4 NFE exome

AF:

0.736

Gnomad4 OTH exome

AF:

0.737

GnomAD4 genome

AF:

0.770

AC:

117150

AN:

152182

Hom.:

45451

Cov.:

AF XY:

0.766

AC XY:

56942

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.876

Gnomad4 AMR

AF:

0.722

Gnomad4 ASJ

AF:

0.773

Gnomad4 EAS

AF:

0.575

Gnomad4 SAS

AF:

0.724

Gnomad4 FIN

AF:

0.705

Gnomad4 NFE

AF:

0.743

Gnomad4 OTH

AF:

0.768

Alfa

AF:

0.740

Hom.:

5219

Bravo

AF:

0.775

Asia WGS

AF:

0.657

AC:

2286

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.95

CADD

Benign

0.36

DANN

Benign

0.41

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