chr7-37876853-A-G

Position:

• chr7-37876853-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016616.5(NME8):​c.840A>G​(p.Arg280Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 1,610,984 control chromosomes in the GnomAD database, including 10,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1896 hom., cov: 32)
  • Exomes 𝑓: 0.093 (8469 hom.)
• Consequence: NME8 NM_016616.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.316

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]

ENSG00000290149 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-37876853-A-G is Benign according to our data. Variant chr7-37876853-A-G is described in ClinVar as [Benign]. Clinvar id is 164802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.316 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NME8	NM_016616.5	c.840A>G	p.Arg280Arg	synonymous_variant	12/18	ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9	c.840A>G	p.Arg280Arg	synonymous_variant	12/18	1	NM_016616.5	ENSP00000199447.4
NME8	ENST00000440017.5	c.840A>G	p.Arg280Arg	synonymous_variant	11/16	1		ENSP00000397063.1
ENSG00000290149	ENST00000476620.1	c.-38+19508A>G		intron_variant		4		ENSP00000425858.1
NME8	ENST00000426106.1	n.106-7450A>G		intron_variant		5		ENSP00000408841.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21038 AN: 151980 Hom.: 1887 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.122 AC: 30433 AN: 250106 Hom.: 2407 AF XY: 0.123 AC XY: 16567 AN XY: 135194

Gnomad AFR exome AF: 0.238

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.0615

Gnomad EAS exome AF: 0.198

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0735

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0933 AC: 136071 AN: 1458886 Hom.: 8469 Cov.: 30 AF XY: 0.0965 AC XY: 70030 AN XY: 725802

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.0590

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0727

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.138 AC: 21060 AN: 152098 Hom.: 1896 Cov.: 32 AF XY: 0.146 AC XY: 10854 AN XY: 74354

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0723

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0992 Hom.: 589

Bravo AF: 0.137

Asia WGS AF: 0.205 AC: 713 AN: 3474

EpiCase AF: 0.0701

EpiControl AF: 0.0676

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Arg280Arg in exon 12 of TXNDC3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 22.9% (1011/4406) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs62001868). -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2014

This alteration is classified as 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Primary ciliary dyskinesia 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs62001868; hg19: chr7-37916455;