Variant rs2249451 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016616.5(NME8):c.271-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,142,696 control chromosomes in the GnomAD database, including 483,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64209 hom., cov: 32)

Exomes 𝑓: 0.92 ( 419768 hom. )

Consequence

NME8
NM_016616.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.767

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:

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 (BayesDel_noAF=-0.93).

BP6

Variant 7-37861979-G-A is Benign according to our data. Variant chr7-37861979-G-A is described in ClinVar as [Benign]. Clinvar id is 260759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NME8	NM_016616.5 linkuse as main transcript	c.271-49G>A		intron_variant		ENST00000199447.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME8	ENST00000199447.9 linkuse as main transcript	c.271-49G>A		intron_variant		1	NM_016616.5	P1

Frequencies

GnomAD3 genomes

AF:

0.916

AC:

139411

AN:

152122

Hom.:

64161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.921

Gnomad AMI

AF:

0.958

Gnomad AMR

AF:

0.902

Gnomad ASJ

AF:

0.967

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.817

Gnomad FIN

AF:

0.844

Gnomad MID

AF:

0.952

Gnomad NFE

AF:

0.948

Gnomad OTH

AF:

0.926

GnomAD3 exomes

AF:

0.886

AC:

221766

AN:

250426

Hom.:

99087

AF XY:

0.887

AC XY:

120114

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.917

Gnomad AMR exome

AF:

0.813

Gnomad ASJ exome

AF:

0.964

Gnomad EAS exome

AF:

0.690

Gnomad SAS exome

AF:

0.828

Gnomad FIN exome

AF:

0.861

Gnomad NFE exome

AF:

0.947

Gnomad OTH exome

AF:

0.913

GnomAD4 exome

AF:

0.918

AC:

909538

AN:

990454

Hom.:

419768

Cov.:

AF XY:

0.916

AC XY:

471001

AN XY:

513960

show subpopulations

Gnomad4 AFR exome

AF:

0.919

Gnomad4 AMR exome

AF:

0.825

Gnomad4 ASJ exome

AF:

0.963

Gnomad4 EAS exome

AF:

0.710

Gnomad4 SAS exome

AF:

0.831

Gnomad4 FIN exome

AF:

0.867

Gnomad4 NFE exome

AF:

0.948

Gnomad4 OTH exome

AF:

0.917

GnomAD4 genome

AF:

0.916

AC:

139518

AN:

152242

Hom.:

64209

Cov.:

AF XY:

0.908

AC XY:

67601

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.921

Gnomad4 AMR

AF:

0.902

Gnomad4 ASJ

AF:

0.967

Gnomad4 EAS

AF:

0.693

Gnomad4 SAS

AF:

0.817

Gnomad4 FIN

AF:

0.844

Gnomad4 NFE

AF:

0.948

Gnomad4 OTH

AF:

0.926

Alfa

AF:

0.934

Hom.:

28257

Bravo

AF:

0.918

Asia WGS

AF:

0.762

AC:

2652

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.1

DANN

Benign

0.29

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