rs2722371

chr7-37850479-G-Achr7-37850479-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016616.5(NME8):c.91+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,606,318 control chromosomes in the GnomAD database, including 50,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6012 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44124 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.118

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 7-37850479-G-A is Benign according to our data. Variant chr7-37850479-G-A is described in ClinVar as [Benign]. Clinvar id is 260770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NME8	NM_016616.5	c.91+44G>A		intron_variant		ENST00000199447.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME8	ENST00000199447.9	c.91+44G>A		intron_variant		1	NM_016616.5	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41820 AN: 151976 Hom.: 6001 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.258

GnomAD3 exomes AF: 0.230 AC: 57508 AN: 250452 Hom.: 7109 AF XY: 0.224 AC XY: 30357 AN XY: 135380

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.185

Gnomad SAS exome AF: 0.137

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.242 AC: 352597 AN: 1454226 Hom.: 44124 Cov.: 29 AF XY: 0.240 AC XY: 173444 AN XY: 723934

Gnomad4 AFR exome AF: 0.371

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.275 AC: 41863 AN: 152092 Hom.: 6012 Cov.: 32 AF XY: 0.272 AC XY: 20229 AN XY: 74338

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.257

Alfa AF: 0.251 Hom.: 7901

Bravo AF: 0.277

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.67
Dann	Benign	0.33

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: rs2722371; hg19: chr7-37890081; COSMIC: COSV52250741;