1-169230187-C-T

Variant names:

• chr1-169230187-C-T
• rs6703463
• NM_013330.5:c.990+531G>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.990+531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,718 control chromosomes in the GnomAD database, including 11,498 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 0.38 (11498 hom., cov: 31)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME7	NM_013330.5	c.990+531G>A		intron_variant	Intron 10 of 11	ENST00000367811.8	NP_037462.1
NME7	NM_197972.3	c.882+531G>A		intron_variant	Intron 10 of 11		NP_932076.1
NME7	NR_104229.2	n.1077+531G>A		intron_variant	Intron 10 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME7	ENST00000367811.8	c.990+531G>A		intron_variant	Intron 10 of 11	1	NM_013330.5	ENSP00000356785.3

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57206 AN: 151602 Hom.: 11493 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.377 AC: 57251 AN: 151718 Hom.: 11498 Cov.: 31 AF XY: 0.379 AC XY: 28116 AN XY: 74108

African (AFR) AF: 0.277 AC: 11459 AN: 41328

American (AMR) AF: 0.345 AC: 5257 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1460 AN: 3468

East Asian (EAS) AF: 0.787 AC: 4058 AN: 5156

South Asian (SAS) AF: 0.330 AC: 1589 AN: 4810

European-Finnish (FIN) AF: 0.446 AC: 4674 AN: 10476

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27347 AN: 67916

Other (OTH) AF: 0.393 AC: 827 AN: 2104

Alfa AF: 0.357 Hom.: 5140

Bravo AF: 0.370

Asia WGS AF: 0.513 AC: 1782 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.42
PhyloP100		-0.63
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: rs6703463; hg19: chr1-169199425;