rs3841582

Variant names:

• chr7-37864463-TAAC-T
• rs3841582
• NM_016616.5:c.528+46_528+48delAAC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016616.5(NME8):​c.528+46_528+48delAAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,454,704 control chromosomes in the GnomAD database, including 264,824 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (21695 hom., cov: 0)
  • Exomes 𝑓: 0.60 (243129 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.287
• Publications: 3 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 -10 ACMG points.

• BP6: Variant 7-37864463-TAAC-T is Benign according to our data. Variant chr7-37864463-TAAC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 260763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5	c.528+46_528+48delAAC		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+43_528+45delAAC		intron_variant	Intron 9 of 17	1	NM_016616.5	ENSP00000199447.4
ENSG00000290149	ENST00000476620.1	c.-38+7119_-38+7121delAAC		intron_variant	Intron 2 of 3	4		ENSP00000425858.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78617 AN: 151546 Hom.: 21687 Cov.: 0

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.540

GnomAD2 exomes AF: 0.548 AC: 103513 AN: 188764 AF XY: 0.563

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.574

Gnomad EAS exome AF: 0.351

Gnomad FIN exome AF: 0.602

Gnomad NFE exome AF: 0.638

Gnomad OTH exome AF: 0.569

GnomAD4 exome AF: 0.602 AC: 784204 AN: 1303040 Hom.: 243129 AF XY: 0.604 AC XY: 391301 AN XY: 647348

African (AFR) AF: 0.304 AC: 9202 AN: 30242

American (AMR) AF: 0.386 AC: 14879 AN: 38576

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 13685 AN: 23876

East Asian (EAS) AF: 0.362 AC: 13059 AN: 36060

South Asian (SAS) AF: 0.624 AC: 49031 AN: 78596

European-Finnish (FIN) AF: 0.602 AC: 28902 AN: 47986

Middle Eastern (MID) AF: 0.575 AC: 2518 AN: 4382

European-Non Finnish (NFE) AF: 0.628 AC: 621553 AN: 989166

Other (OTH) AF: 0.579 AC: 31375 AN: 54156

GnomAD4 genome AF: 0.519 AC: 78650 AN: 151664 Hom.: 21695 Cov.: 0 AF XY: 0.517 AC XY: 38259 AN XY: 74066

African (AFR) AF: 0.324 AC: 13401 AN: 41376

American (AMR) AF: 0.462 AC: 7035 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2013 AN: 3464

East Asian (EAS) AF: 0.362 AC: 1871 AN: 5162

South Asian (SAS) AF: 0.609 AC: 2927 AN: 4810

European-Finnish (FIN) AF: 0.582 AC: 6099 AN: 10480

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43309 AN: 67828

Other (OTH) AF: 0.541 AC: 1142 AN: 2110

Alfa AF: 0.586 Hom.: 4909

Bravo AF: 0.498

Asia WGS AF: 0.473 AC: 1643 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.29
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: rs3841582; hg19: chr7-37904065;