7-37885135-T-G

Position:

• chr7-37885135-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000290149 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 164804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-37885135-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NME8	NM_016616.5	c.1140-10T>G		intron_variant		ENST00000199447.9	NP_057700.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NME8	ENST00000199447.9	c.1140-10T>G		intron_variant		1	NM_016616.5	ENSP00000199447.4
NME8	ENST00000440017.5	c.1140-10T>G		intron_variant		1		ENSP00000397063.1
ENSG00000290149	ENST00000476620.1	c.-38+27790T>G		intron_variant		4		ENSP00000425858.1
NME8	ENST00000426106.1	n.*86-10T>G		intron_variant		5		ENSP00000408841.1

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

GnomAD3 exomes AF: 0.509 AC: 125665 AN: 246962 Hom.: 33112 AF XY: 0.510 AC XY: 68022 AN XY: 133422

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 SAS exome AF: 0.608

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

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.356

Gnomad4 EAS exome AF: 0.735

Gnomad4 SAS exome AF: 0.604

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.495

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

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.449

Alfa AF: 0.457 Hom.: 18464

Bravo AF: 0.461

Asia WGS AF: 0.648 AC: 2254 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	1140-10T>G in intron 13 of TXNDC3: This variant is not expected to have clinical significance because it has been identified in 46.9% (4032/8598) of European Am erican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1530822). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 6 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.7
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs1530822; hg19: chr7-37924737;