7-37864302-C-T

Variant names:

• chr7-37864302-C-T
• rs3816418
• NM_016616.5:c.455-46C>T

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.455-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,555,418 control chromosomes in the GnomAD database, including 424,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45451 hom., cov: 33)
  • Exomes 𝑓: 0.73 (378968 hom.)
• Consequence: NME8 NM_016616.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.581
• Publications: 4 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=-0.95).
• BP6: Variant 7-37864302-C-T is Benign according to our data. Variant chr7-37864302-C-T is described in ClinVar as [Benign]. Clinvar id is 260762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME8	NM_016616.5	c.455-46C>T		intron_variant	Intron 8 of 17	ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9	c.455-46C>T		intron_variant	Intron 8 of 17	1	NM_016616.5	ENSP00000199447.4
ENSG00000290149	ENST00000476620.1	c.-38+6957C>T		intron_variant	Intron 2 of 3	4		ENSP00000425858.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117044 AN: 152062 Hom.: 45402 Cov.: 33

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.770

GnomAD2 exomes AF: 0.726 AC: 152607 AN: 210182 AF XY: 0.727

Gnomad AFR exome AF: 0.879

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.773

Gnomad EAS exome AF: 0.563

Gnomad FIN exome AF: 0.717

Gnomad NFE exome AF: 0.747

Gnomad OTH exome AF: 0.741

GnomAD4 exome AF: 0.733 AC: 1029169 AN: 1403236 Hom.: 378968 Cov.: 34 AF XY: 0.733 AC XY: 509729 AN XY: 694946

African (AFR) AF: 0.882 AC: 28469 AN: 32282

American (AMR) AF: 0.678 AC: 27483 AN: 40514

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 19155 AN: 24682

East Asian (EAS) AF: 0.569 AC: 21512 AN: 37798

South Asian (SAS) AF: 0.737 AC: 60680 AN: 82364

European-Finnish (FIN) AF: 0.720 AC: 36006 AN: 50038

Middle Eastern (MID) AF: 0.759 AC: 4240 AN: 5586

European-Non Finnish (NFE) AF: 0.736 AC: 789146 AN: 1072342

Other (OTH) AF: 0.737 AC: 42478 AN: 57630

GnomAD4 genome AF: 0.770 AC: 117150 AN: 152182 Hom.: 45451 Cov.: 33 AF XY: 0.766 AC XY: 56942 AN XY: 74382

African (AFR) AF: 0.876 AC: 36411 AN: 41544

American (AMR) AF: 0.722 AC: 11041 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2684 AN: 3472

East Asian (EAS) AF: 0.575 AC: 2974 AN: 5176

South Asian (SAS) AF: 0.724 AC: 3490 AN: 4820

European-Finnish (FIN) AF: 0.705 AC: 7447 AN: 10568

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50521 AN: 68004

Other (OTH) AF: 0.768 AC: 1623 AN: 2112

Alfa AF: 0.740 Hom.: 5219

Bravo AF: 0.775

Asia WGS AF: 0.657 AC: 2286 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.41
PhyloP100		-0.58
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: rs3816418; hg19: chr7-37903904; COSMIC: COSV52250065;