NM_013330.5:c.755-22219G>A

Variant names:

• chr1-169259906-C-T
• rs16828170
• NM_013330.5:c.755-22219G>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.755-22219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 132,426 control chromosomes in the GnomAD database, including 4,653 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 0.14 (4653 hom., cov: 21)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013330.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME7	NM_013330.5	MANE Select	c.755-22219G>A		intron	N/A	NP_037462.1
	NME7	NM_197972.3		c.647-22219G>A		intron	N/A	NP_932076.1
	NME7	NR_104229.2		n.842-22219G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME7	ENST00000367811.8	TSL:1 MANE Select	c.755-22219G>A		intron	N/A	ENSP00000356785.3
	NME7	ENST00000472647.5	TSL:2	c.647-22219G>A		intron	N/A	ENSP00000433341.1
	NME7	ENST00000480478.5	TSL:5	n.567-22219G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.142 AC: 18841 AN: 132316 Hom.: 4645 Cov.: 21

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0684

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0846

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.143 AC: 18887 AN: 132426 Hom.: 4653 Cov.: 21 AF XY: 0.141 AC XY: 9061 AN XY: 64412

African (AFR) AF: 0.130 AC: 5121 AN: 39386

American (AMR) AF: 0.156 AC: 2112 AN: 13530

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 318 AN: 2912

East Asian (EAS) AF: 0.129 AC: 643 AN: 4980

South Asian (SAS) AF: 0.0698 AC: 302 AN: 4326

European-Finnish (FIN) AF: 0.174 AC: 1463 AN: 8410

Middle Eastern (MID) AF: 0.0906 AC: 23 AN: 254

European-Non Finnish (NFE) AF: 0.154 AC: 8634 AN: 56212

Other (OTH) AF: 0.114 AC: 204 AN: 1786

Alfa AF: 0.134 Hom.: 455

Asia WGS AF: 0.103 AC: 350 AN: 3370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.23
PhyloP100		-0.46
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: rs16828170; hg19: chr1-169229144;