NM_016616.5:c.1140-10T>G

Variant names:

• chr7-37885135-T-G
• rs1530822
• NM_016616.5:c.1140-10T>G

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.1140-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,576,702 control chromosomes in the GnomAD database, including 192,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17123 hom., cov: 32)
  • Exomes 𝑓: 0.49 (174999 hom.)
• Consequence: NME8 NM_016616.5 intron
• Scores: Splicing: ADA: 0.001191
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0160
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-37885135-T-G is Benign according to our data. Variant chr7-37885135-T-G is described in ClinVar as Benign. ClinVar VariationId is 164804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME8	NM_016616.5	MANE Select	c.1140-10T>G		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.1140-10T>G		intron	N/A	ENSP00000199447.4	Q8N427
	NME8	ENST00000440017.5	TSL:1	c.1140-10T>G		intron	N/A	ENSP00000397063.1	Q8N427
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-38+27790T>G		intron	N/A	ENSP00000425858.1	D6RIH7

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71154 AN: 151880 Hom.: 17104 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.454

GnomAD2 exomes AF: 0.509 AC: 125665 AN: 246962 AF XY: 0.510

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.528

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.744

Gnomad FIN exome AF: 0.527

Gnomad NFE exome AF: 0.468

Gnomad OTH exome AF: 0.480

GnomAD4 exome AF: 0.490 AC: 698578 AN: 1424704 Hom.: 174999 Cov.: 24 AF XY: 0.493 AC XY: 350194 AN XY: 711044

African (AFR) AF: 0.388 AC: 12692 AN: 32738

American (AMR) AF: 0.525 AC: 23276 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 9214 AN: 25870

East Asian (EAS) AF: 0.735 AC: 28945 AN: 39394

South Asian (SAS) AF: 0.604 AC: 51530 AN: 85246

European-Finnish (FIN) AF: 0.530 AC: 28194 AN: 53218

Middle Eastern (MID) AF: 0.391 AC: 2220 AN: 5684

European-Non Finnish (NFE) AF: 0.476 AC: 513247 AN: 1079116

Other (OTH) AF: 0.495 AC: 29260 AN: 59106

GnomAD4 genome AF: 0.468 AC: 71200 AN: 151998 Hom.: 17123 Cov.: 32 AF XY: 0.477 AC XY: 35435 AN XY: 74296

African (AFR) AF: 0.389 AC: 16121 AN: 41458

American (AMR) AF: 0.523 AC: 7981 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1213 AN: 3472

East Asian (EAS) AF: 0.738 AC: 3809 AN: 5164

South Asian (SAS) AF: 0.617 AC: 2971 AN: 4816

European-Finnish (FIN) AF: 0.537 AC: 5671 AN: 10570

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32010 AN: 67934

Other (OTH) AF: 0.449 AC: 950 AN: 2114

Alfa AF: 0.456 Hom.: 23251

Bravo AF: 0.461

Asia WGS AF: 0.648 AC: 2254 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.7
DANN	Benign	0.89
PhyloP100		0.016
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.068
SpliceAI score (max)		0.050		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: rs1530822; hg19: chr7-37924737; COSMIC: COSV107214062;