rs73340816

Variant names:

• chr7-37877026-A-G
• rs73340816
• NM_016616.5:c.994+19A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016616.5(NME8):​c.994+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,594,754 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (4 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0270
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• primary ciliary dyskinesia 6

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-37877026-A-G is Benign according to our data. Variant chr7-37877026-A-G is described in ClinVar as Benign. ClinVar VariationId is 260771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00628 (956/152344) while in subpopulation AFR AF = 0.0177 (738/41586). AF 95% confidence interval is 0.0167. There are 5 homozygotes in GnomAd4. There are 485 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5	c.994+19A>G		intron_variant	Intron 12 of 17	ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9	c.994+19A>G		intron_variant	Intron 12 of 17	1	NM_016616.5	ENSP00000199447.4
NME8	ENST00000440017.5	c.994+19A>G		intron_variant	Intron 11 of 15	1		ENSP00000397063.1
ENSG00000290149	ENST00000476620.1	c.-38+19681A>G		intron_variant	Intron 2 of 3	4		ENSP00000425858.1
NME8	ENST00000426106.1	n.106-7277A>G		intron_variant	Intron 2 of 4	5		ENSP00000408841.1

Frequencies

GnomAD3 genomes AF: 0.00628 AC: 956 AN: 152226 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00877

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00910

GnomAD2 exomes AF: 0.00239 AC: 596 AN: 249070 AF XY: 0.00205

Gnomad AFR exome AF: 0.0183

Gnomad AMR exome AF: 0.00462

Gnomad ASJ exome AF: 0.000399

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00104

Gnomad OTH exome AF: 0.00363

GnomAD4 exome AF: 0.00126 AC: 1813 AN: 1442410 Hom.: 4 Cov.: 27 AF XY: 0.00123 AC XY: 886 AN XY: 718946

African (AFR) AF: 0.0172 AC: 568 AN: 33028

American (AMR) AF: 0.00518 AC: 231 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.000385 AC: 10 AN: 25978

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39368

South Asian (SAS) AF: 0.000117 AC: 10 AN: 85770

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53318

Middle Eastern (MID) AF: 0.00736 AC: 40 AN: 5436

European-Non Finnish (NFE) AF: 0.000696 AC: 762 AN: 1095254

Other (OTH) AF: 0.00319 AC: 190 AN: 59632

GnomAD4 genome AF: 0.00628 AC: 956 AN: 152344 Hom.: 5 Cov.: 32 AF XY: 0.00651 AC XY: 485 AN XY: 74498

African (AFR) AF: 0.0177 AC: 738 AN: 41586

American (AMR) AF: 0.00876 AC: 134 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68026

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00354 Hom.: 1

Bravo AF: 0.00753

Asia WGS AF: 0.00202 AC: 8 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Primary ciliary dyskinesia 6 Benign:1

Jan 30, 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	-0.75
CADD	Benign	3.8
DANN	Benign	0.85
PhyloP100		-0.027
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73340816; hg19: chr7-37916628;