Variant 7-37885277-A-G 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.1247+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,427,886 control chromosomes in the GnomAD database, including 174,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17128 hom., cov: 32)

Exomes 𝑓: 0.49 ( 157041 hom. )

Consequence

NME8
NM_016616.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.02

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=-0.88).

BP6

Variant 7-37885277-A-G is Benign according to our data. Variant chr7-37885277-A-G is described in ClinVar as [Benign]. Clinvar id is 260754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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.1247+25A>G		intron_variant		ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
NME8	ENST00000199447.9 linkuse as main transcript	c.1247+25A>G	intron_variant	1	NM_016616.5	ENSP00000199447	P1
NME8	ENST00000440017.5 linkuse as main transcript	c.1247+25A>G	intron_variant	1		ENSP00000397063	P1
NME8	ENST00000426106.1 linkuse as main transcript	c.*193+25A>G	intron_variant, NMD_transcript_variant	5		ENSP00000408841

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71174

AN:

151884

Hom.:

17109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.737

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.455

GnomAD3 exomes

AF:

0.510

AC:

123409

AN:

242034

Hom.:

32488

AF XY:

0.511

AC XY:

66783

AN XY:

130682

show subpopulations

Gnomad AFR exome

AF:

0.381

Gnomad AMR exome

AF:

0.528

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.744

Gnomad SAS exome

AF:

0.610

Gnomad FIN exome

AF:

0.527

Gnomad NFE exome

AF:

0.469

Gnomad OTH exome

AF:

0.480

GnomAD4 exome

AF:

0.489

AC:

623773

AN:

1275884

Hom.:

157041

Cov.:

AF XY:

0.492

AC XY:

316562

AN XY:

644070

show subpopulations

Gnomad4 AFR exome

AF:

0.385

Gnomad4 AMR exome

AF:

0.525

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.734

Gnomad4 SAS exome

AF:

0.604

Gnomad4 FIN exome

AF:

0.530

Gnomad4 NFE exome

AF:

0.472

Gnomad4 OTH exome

AF:

0.494

GnomAD4 genome

AF:

0.469

AC:

71220

AN:

152002

Hom.:

17128

Cov.:

AF XY:

0.477

AC XY:

35440

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.389

Gnomad4 AMR

AF:

0.523

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.737

Gnomad4 SAS

AF:

0.617

Gnomad4 FIN

AF:

0.537

Gnomad4 NFE

AF:

0.471

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.377

Hom.:

2141

Bravo

AF:

0.461

Asia WGS

AF:

0.648

AC:

2253

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Primary ciliary dyskinesia 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.2

DANN

Benign

0.64

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