rs1200082

Variant names:

• chr1-169191488-G-T
• rs1200082
• NM_013330.5:c.991-21934C>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.991-21934C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,244 control chromosomes in the GnomAD database, including 58,845 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 0.88 (58845 hom., cov: 32)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME7	NM_013330.5	MANE Select	c.991-21934C>A		intron	N/A	NP_037462.1	Q9Y5B8-1
	NME7	NM_197972.3		c.883-21934C>A		intron	N/A	NP_932076.1	Q9Y5B8-2
	NME7	NR_104229.2		n.1078-783C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME7	ENST00000367811.8	TSL:1 MANE Select	c.991-21934C>A		intron	N/A	ENSP00000356785.3	Q9Y5B8-1
	NME7	ENST00000961401.1		c.1072-21934C>A		intron	N/A	ENSP00000631460.1
	NME7	ENST00000856223.1		c.940-21934C>A		intron	N/A	ENSP00000526282.1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133284 AN: 152126 Hom.: 58783 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.879

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

GnomAD4 genome AF: 0.876 AC: 133406 AN: 152244 Hom.: 58845 Cov.: 32 AF XY: 0.877 AC XY: 65280 AN XY: 74436

African (AFR) AF: 0.967 AC: 40210 AN: 41574

American (AMR) AF: 0.898 AC: 13723 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3151 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5171 AN: 5186

South Asian (SAS) AF: 0.811 AC: 3910 AN: 4822

European-Finnish (FIN) AF: 0.849 AC: 8995 AN: 10594

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55420 AN: 67990

Other (OTH) AF: 0.881 AC: 1862 AN: 2114

Alfa AF: 0.855 Hom.: 47266

Bravo AF: 0.887

Asia WGS AF: 0.927 AC: 3223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.7
DANN	Benign	0.32
PhyloP100		1.1
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: rs1200082; hg19: chr1-169160726;