rs3213976

Variant names:

• chr7-37857294-G-A
• rs3213976
• NM_016616.5:c.219G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-37857294-G-A
• chr7-37857294-G-C
• chr7-37857294-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_016616.5(NME8):​c.219G>A​(p.Val73Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,608,500 control chromosomes in the GnomAD database, including 9,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (670 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9177 hom.)
• Consequence: NME8 NM_016616.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.131

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 -16 ACMG points.

• BP6: Variant 7-37857294-G-A is Benign according to our data. Variant chr7-37857294-G-A is described in ClinVar as [Benign]. Clinvar id is 164800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5	c.219G>A	p.Val73Val	synonymous_variant	Exon 6 of 18	ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9	c.219G>A	p.Val73Val	synonymous_variant	Exon 6 of 18	1	NM_016616.5	ENSP00000199447.4
ENSG00000290149	ENST00000476620	c.-89G>A		5_prime_UTR_variant	Exon 2 of 4	4		ENSP00000425858.1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13306 AN: 152054 Hom.: 670 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.0877

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0909

GnomAD3 exomes AF: 0.0973 AC: 24372 AN: 250440 Hom.: 1312 AF XY: 0.0976 AC XY: 13207 AN XY: 135324

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.0755

Gnomad SAS exome AF: 0.0598

Gnomad FIN exome AF: 0.0831

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.109 AC: 158478 AN: 1456328 Hom.: 9177 Cov.: 29 AF XY: 0.108 AC XY: 78170 AN XY: 724612

Gnomad4 AFR exome AF: 0.0222

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.0861

Gnomad4 SAS exome AF: 0.0620

Gnomad4 FIN exome AF: 0.0855

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0874 AC: 13305 AN: 152172 Hom.: 670 Cov.: 32 AF XY: 0.0870 AC XY: 6473 AN XY: 74386

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0757

Gnomad4 SAS AF: 0.0568

Gnomad4 FIN AF: 0.0877

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0923

Alfa AF: 0.110 Hom.: 1222

Bravo AF: 0.0868

Asia WGS AF: 0.0680 AC: 237 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Val73Val in exon 6 of TXNDC3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 10.9% (940/8598) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs3213976). -

Primary ciliary dyskinesia Benign:1

Dec 11, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 6 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.70
CADD	Benign	4.1
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: -20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3213976; hg19: chr7-37896896; COSMIC: COSV52250638;