7-37850236-TTTTC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016616.5(NME8):c.-7-16_-7-13del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,595,572 control chromosomes in the GnomAD database, including 49,317 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5899 hom., cov: 20)
  • Exomes 𝑓: 0.24 (43418 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.47

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 -10 ACMG points.

• BP6: Variant 7-37850236-TTTTC-T is Benign according to our data. Variant chr7-37850236-TTTTC-T is described in ClinVar as [Benign]. Clinvar id is 1278890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-37850236-TTTTC-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NME8	NM_016616.5	c.-7-16_-7-13del		intron_variant		ENST00000199447.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME8	ENST00000199447.9	c.-7-16_-7-13del		intron_variant		1	NM_016616.5	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41564 AN: 151724 Hom.: 5887 Cov.: 20

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.257

GnomAD3 exomes AF: 0.229 AC: 57440 AN: 250454 Hom.: 7089 AF XY: 0.224 AC XY: 30338 AN XY: 135410

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: 0.136

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.240 AC: 346593 AN: 1443728 Hom.: 43418 AF XY: 0.237 AC XY: 170757 AN XY: 719236

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.274 AC: 41609 AN: 151844 Hom.: 5899 Cov.: 20 AF XY: 0.271 AC XY: 20072 AN XY: 74196

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.256

Alfa AF: 0.264 Hom.: 998

Bravo AF: 0.277

Asia WGS AF: 0.163 AC: 569 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 27, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs141149150; hg19: chr7-37889838;