NM_013330.5:c.649-1660G>A

Variant names:

• chr1-169289068-C-T
• rs12121994
• NM_013330.5:c.649-1660G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013330.5(NME7):​c.649-1660G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,986 control chromosomes in the GnomAD database, including 8,398 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8398 hom., cov: 32)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 8 publications found

Genes affected

NME7 (HGNC:20461): (NME/NM23 family member 7) This gene encodes a member of the non-metastatic expressed family of nucleoside diphosphate kinases. Members of this family are enzymes that catalyzes phosphate transfer from nucleoside triphosphates to nucleoside diphosphates. This protein contains two kinase domains, one of which is involved in autophosphorylation and the other may be inactive. This protein localizes to the centrosome and functions as a component of the gamma-tubulin ring complex which plays a role in microtubule organization. Mutations in this gene may be associated with venous thromboembolism. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ATP1B1 (HGNC:804): (ATPase Na+/K+ transporting subunit beta 1) The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes a beta 1 subunit. Alternatively spliced transcript variants encoding different isoforms have been described, but their biological validity is not known. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME7	NM_013330.5	c.649-1660G>A		intron_variant	Intron 6 of 11	ENST00000367811.8	NP_037462.1
NME7	NM_197972.3	c.541-1660G>A		intron_variant	Intron 6 of 11		NP_932076.1
NME7	NR_104229.2	n.736-1660G>A		intron_variant	Intron 6 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME7	ENST00000367811.8	c.649-1660G>A		intron_variant	Intron 6 of 11	1	NM_013330.5	ENSP00000356785.3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47825 AN: 151868 Hom.: 8395 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.322

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.315 AC: 47851 AN: 151986 Hom.: 8398 Cov.: 32 AF XY: 0.318 AC XY: 23632 AN XY: 74296

African (AFR) AF: 0.182 AC: 7570 AN: 41488

American (AMR) AF: 0.292 AC: 4446 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3468

East Asian (EAS) AF: 0.666 AC: 3435 AN: 5158

South Asian (SAS) AF: 0.250 AC: 1202 AN: 4810

European-Finnish (FIN) AF: 0.441 AC: 4657 AN: 10552

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24257 AN: 67942

Other (OTH) AF: 0.326 AC: 688 AN: 2112

Alfa AF: 0.332 Hom.: 4489

Bravo AF: 0.303

Asia WGS AF: 0.420 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-0.39
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: rs12121994; hg19: chr1-169258306;