rs117681493

Variant names:

• chr7-37864432-T-C
• rs117681493
• NM_016616.5:c.528+11T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_016616.5(NME8):​c.528+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,559,612 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (50 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.08
• Publications: 1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 7-37864432-T-C is Benign according to our data. Variant chr7-37864432-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	NM_016616.5	MANE Select	c.528+11T>C		intron	N/A	NP_057700.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	ENST00000199447.9	TSL:1 MANE Select	c.528+11T>C		intron	N/A	ENSP00000199447.4	Q8N427
	NME8	ENST00000440017.5	TSL:1	c.528+11T>C		intron	N/A	ENSP00000397063.1	Q8N427
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-38+7087T>C		intron	N/A	ENSP00000425858.1	D6RIH7

Frequencies

GnomAD3 genomes AF: 0.00448 AC: 674 AN: 150392 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.0145

Gnomad AMR AF: 0.00180

Gnomad ASJ AF: 0.00493

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00151

Gnomad FIN AF: 0.00536

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00743

Gnomad OTH AF: 0.00295

GnomAD2 exomes AF: 0.00480 AC: 1101 AN: 229224 AF XY: 0.00509

Gnomad AFR exome AF: 0.000812

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00337

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00423

Gnomad NFE exome AF: 0.00829

Gnomad OTH exome AF: 0.00267

GnomAD4 exome AF: 0.00669 AC: 9421 AN: 1409104 Hom.: 50 Cov.: 32 AF XY: 0.00646 AC XY: 4527 AN XY: 700538

African (AFR) AF: 0.000742 AC: 24 AN: 32366

American (AMR) AF: 0.00121 AC: 52 AN: 42906

Ashkenazi Jewish (ASJ) AF: 0.00336 AC: 84 AN: 25006

East Asian (EAS) AF: 0.00 AC: 0 AN: 38552

South Asian (SAS) AF: 0.00271 AC: 227 AN: 83830

European-Finnish (FIN) AF: 0.00488 AC: 251 AN: 51412

Middle Eastern (MID) AF: 0.000551 AC: 3 AN: 5444

European-Non Finnish (NFE) AF: 0.00794 AC: 8512 AN: 1071612

Other (OTH) AF: 0.00462 AC: 268 AN: 57976

GnomAD4 genome AF: 0.00448 AC: 674 AN: 150508 Hom.: 2 Cov.: 33 AF XY: 0.00414 AC XY: 304 AN XY: 73362

African (AFR) AF: 0.00114 AC: 47 AN: 41246

American (AMR) AF: 0.00180 AC: 27 AN: 15000

Ashkenazi Jewish (ASJ) AF: 0.00493 AC: 17 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00151 AC: 7 AN: 4622

European-Finnish (FIN) AF: 0.00536 AC: 55 AN: 10266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00743 AC: 502 AN: 67542

Other (OTH) AF: 0.00292 AC: 6 AN: 2056

Alfa AF: 0.00519 Hom.: 2

Bravo AF: 0.00442

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Primary ciliary dyskinesia 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		1.1
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs117681493; hg19: chr7-37904034;