Variant rs117681493 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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 [Likely_benign]. Clinvar id is 178810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NME8	NM_016616.5 linkuse as main transcript	c.528+11T>C		intron_variant		ENST00000199447.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME8	ENST00000199447.9 linkuse as main transcript	c.528+11T>C		intron_variant		1	NM_016616.5	P1

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

GnomAD3 exomes

AF:

0.00480

AC:

1101

AN:

229224

Hom.:

AF XY:

0.00509

AC XY:

633

AN XY:

124390

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 SAS exome

AF:

0.00262

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

Gnomad4 AFR exome

AF:

0.000742

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00336

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00271

Gnomad4 FIN exome

AF:

0.00488

Gnomad4 NFE exome

AF:

0.00794

Gnomad4 OTH exome

AF:

0.00462

GnomAD4 genome

AF:

0.00448

AC:

674

AN:

150508

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

304

AN XY:

73362

show subpopulations

Gnomad4 AFR

AF:

0.00114

Gnomad4 AMR

AF:

0.00180

Gnomad4 ASJ

AF:

0.00493

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00151

Gnomad4 FIN

AF:

0.00536

Gnomad4 NFE

AF:

0.00743

Gnomad4 OTH

AF:

0.00292

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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). -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.75

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

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