rs10261071

Variant names:

• chr7-37894632-G-A
• rs10261071
• NM_016616.5:c.1544+22G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016616.5(NME8):​c.1544+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,545,366 control chromosomes in the GnomAD database, including 378,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (32057 hom., cov: 32)
  • Exomes 𝑓: 0.70 (346300 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.04
• Publications: 13 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=-0.92).
• BP6: Variant 7-37894632-G-A is Benign according to our data. Variant chr7-37894632-G-A is described in ClinVar as Benign. ClinVar VariationId is 260756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 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.1544+22G>A		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.1544+22G>A		intron	N/A	ENSP00000199447.4
	NME8	ENST00000440017.5	TSL:1	c.1544+22G>A		intron	N/A	ENSP00000397063.1
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-38+37287G>A		intron	N/A	ENSP00000425858.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97399 AN: 151832 Hom.: 32048 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.652

GnomAD2 exomes AF: 0.641 AC: 147789 AN: 230456 AF XY: 0.647

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.704

Gnomad EAS exome AF: 0.691

Gnomad FIN exome AF: 0.699

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.665

GnomAD4 exome AF: 0.701 AC: 976470 AN: 1393416 Hom.: 346300 Cov.: 28 AF XY: 0.699 AC XY: 485247 AN XY: 694224

African (AFR) AF: 0.498 AC: 16054 AN: 32232

American (AMR) AF: 0.435 AC: 18646 AN: 42824

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 18076 AN: 25446

East Asian (EAS) AF: 0.711 AC: 27486 AN: 38676

South Asian (SAS) AF: 0.592 AC: 49273 AN: 83214

European-Finnish (FIN) AF: 0.704 AC: 37103 AN: 52710

Middle Eastern (MID) AF: 0.691 AC: 3044 AN: 4404

European-Non Finnish (NFE) AF: 0.726 AC: 766982 AN: 1056058

Other (OTH) AF: 0.688 AC: 39806 AN: 57852

GnomAD4 genome AF: 0.641 AC: 97436 AN: 151950 Hom.: 32057 Cov.: 32 AF XY: 0.636 AC XY: 47206 AN XY: 74268

African (AFR) AF: 0.513 AC: 21257 AN: 41400

American (AMR) AF: 0.534 AC: 8143 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2456 AN: 3466

East Asian (EAS) AF: 0.697 AC: 3602 AN: 5166

South Asian (SAS) AF: 0.602 AC: 2906 AN: 4826

European-Finnish (FIN) AF: 0.711 AC: 7518 AN: 10576

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.725 AC: 49272 AN: 67956

Other (OTH) AF: 0.654 AC: 1383 AN: 2116

Alfa AF: 0.677 Hom.: 29561

Bravo AF: 0.623

Asia WGS AF: 0.618 AC: 2146 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.093
DANN	Benign	0.25
PhyloP100		-2.0
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: rs10261071; hg19: chr7-37934234;