rs12118611

Variant names:

• chr1-169306392-A-G
• rs12118611
• NM_013330.5:c.390-3197T>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.390-3197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,130 control chromosomes in the GnomAD database, including 5,474 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 0.24 (5474 hom., cov: 32)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 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.390-3197T>C		intron	N/A	NP_037462.1	Q9Y5B8-1
	NME7	NM_197972.3		c.282-3197T>C		intron	N/A	NP_932076.1	Q9Y5B8-2
	NME7	NR_104229.2		n.477-3197T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME7	ENST00000367811.8	TSL:1 MANE Select	c.390-3197T>C		intron	N/A	ENSP00000356785.3	Q9Y5B8-1
	NME7	ENST00000524967.5	TSL:1	n.452-3197T>C		intron	N/A
	NME7	ENST00000961401.1		c.390-3197T>C		intron	N/A	ENSP00000631460.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36722 AN: 152012 Hom.: 5473 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.241 AC: 36720 AN: 152130 Hom.: 5474 Cov.: 32 AF XY: 0.236 AC XY: 17582 AN XY: 74382

African (AFR) AF: 0.101 AC: 4208 AN: 41508

American (AMR) AF: 0.206 AC: 3144 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 931 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.104 AC: 501 AN: 4826

European-Finnish (FIN) AF: 0.356 AC: 3754 AN: 10556

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23145 AN: 67990

Other (OTH) AF: 0.247 AC: 522 AN: 2114

Alfa AF: 0.292 Hom.: 4066

Bravo AF: 0.227

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.0
DANN	Benign	0.63
PhyloP100		0.42
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: rs12118611; hg19: chr1-169275630;