rs117681493

Variant names:

• chr7-37864432-T-C
• rs117681493
• NM_016616.5:c.528+11T>C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.08

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.

• 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 rank	MANE	Protein	UniProt
NME8	NM_016616.5	c.528+11T>C		intron_variant	Intron 9 of 17	ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9	c.528+11T>C		intron_variant	Intron 9 of 17	1	NM_016616.5	ENSP00000199447.4
ENSG00000290149	ENST00000476620.1	c.-38+7087T>C		intron_variant	Intron 2 of 3	4		ENSP00000425858.1

Frequencies

GnomAD3 genomes AF: 0.00448 AC: 674 AN: 150392 Hom.: 2 Cov.: 33

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.: 5 AF XY: 0.00509 AC XY: 633 AN XY: 124390

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.: 50 Cov.: 32 AF XY: 0.00646 AC XY: 4527 AN XY: 700538

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.: 2 Cov.: 33 AF XY: 0.00414 AC XY: 304 AN XY: 73362

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.: 2

Bravo AF: 0.00442

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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). -

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PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 6 Benign:1

Jan 28, 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	-0.48
CADD	Benign	11
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

Other links and lift over

dbSNP: rs117681493; hg19: chr7-37904034;