rs1200160

Variant names:

• chr1-169133957-A-G
• rs1200160
• NM_013330.5:c.1099-1140T>C

Variant summary

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

The NM_013330.5(NME7):​c.1099-1140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,030 control chromosomes in the GnomAD database, including 18,338 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 0.48 (18338 hom., cov: 32)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME7	NM_013330.5	c.1099-1140T>C		intron_variant	Intron 11 of 11	ENST00000367811.8	NP_037462.1
NME7	NM_197972.3	c.991-1140T>C		intron_variant	Intron 11 of 11		NP_932076.1
NME7	NR_104229.2	n.1249-1140T>C		intron_variant	Intron 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME7	ENST00000367811.8	c.1099-1140T>C		intron_variant	Intron 11 of 11	1	NM_013330.5	ENSP00000356785.3

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73398 AN: 151912 Hom.: 18323 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.483 AC: 73438 AN: 152030 Hom.: 18338 Cov.: 32 AF XY: 0.479 AC XY: 35571 AN XY: 74338

African (AFR) AF: 0.458 AC: 18959 AN: 41410

American (AMR) AF: 0.507 AC: 7753 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1432 AN: 3466

East Asian (EAS) AF: 0.0885 AC: 458 AN: 5176

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4818

European-Finnish (FIN) AF: 0.522 AC: 5532 AN: 10588

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36003 AN: 67970

Other (OTH) AF: 0.489 AC: 1034 AN: 2116

Alfa AF: 0.510 Hom.: 34181

Bravo AF: 0.481

Asia WGS AF: 0.240 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.56
PhyloP100		-0.64
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: rs1200160; hg19: chr1-169103195;