7-37898820-A-G

Variant names:

• chr7-37898820-A-G
• rs10226308
• NM_016616.5:c.*16-1424A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016616.5(NME8):​c.*16-1424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,226 control chromosomes in the GnomAD database, including 1,738 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1738 hom., cov: 32)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 30 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016616.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	NM_016616.5	MANE Select	c.*16-1424A>G		intron	N/A	NP_057700.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	ENST00000199447.9	TSL:1 MANE Select	c.*16-1424A>G		intron	N/A	ENSP00000199447.4
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-38+41475A>G		intron	N/A	ENSP00000425858.1
	NME8	ENST00000476435.1	TSL:1	n.292-1424A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21666 AN: 152108 Hom.: 1736 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0614

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21676 AN: 152226 Hom.: 1738 Cov.: 32 AF XY: 0.139 AC XY: 10355 AN XY: 74422

African (AFR) AF: 0.0827 AC: 3434 AN: 41540

American (AMR) AF: 0.117 AC: 1790 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 681 AN: 3470

East Asian (EAS) AF: 0.0615 AC: 319 AN: 5184

South Asian (SAS) AF: 0.0805 AC: 389 AN: 4830

European-Finnish (FIN) AF: 0.185 AC: 1964 AN: 10602

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12566 AN: 67996

Other (OTH) AF: 0.145 AC: 306 AN: 2106

Alfa AF: 0.165 Hom.: 5524

Bravo AF: 0.134

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.72
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs10226308; hg19: chr7-37938422;