1-169262304-A-G

Variant names:

• chr1-169262304-A-G
• rs12753710
• NM_013330.5:c.755-24617T>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.755-24617T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 134,252 control chromosomes in the GnomAD database, including 3,957 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 0.11 (3957 hom., cov: 22)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 1 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 = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME7	NM_013330.5	c.755-24617T>C		intron_variant	Intron 7 of 11	ENST00000367811.8	NP_037462.1
NME7	NM_197972.3	c.647-24617T>C		intron_variant	Intron 7 of 11		NP_932076.1
NME7	NR_104229.2	n.842-24617T>C		intron_variant	Intron 7 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME7	ENST00000367811.8	c.755-24617T>C		intron_variant	Intron 7 of 11	1	NM_013330.5	ENSP00000356785.3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 15219 AN: 134138 Hom.: 3955 Cov.: 22

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0667

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0750

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.114 AC: 15250 AN: 134252 Hom.: 3957 Cov.: 22 AF XY: 0.122 AC XY: 8014 AN XY: 65520

African (AFR) AF: 0.151 AC: 6023 AN: 39764

American (AMR) AF: 0.119 AC: 1630 AN: 13668

Ashkenazi Jewish (ASJ) AF: 0.0667 AC: 195 AN: 2924

East Asian (EAS) AF: 0.752 AC: 3738 AN: 4970

South Asian (SAS) AF: 0.146 AC: 638 AN: 4368

European-Finnish (FIN) AF: 0.129 AC: 1132 AN: 8756

Middle Eastern (MID) AF: 0.0763 AC: 20 AN: 262

European-Non Finnish (NFE) AF: 0.0288 AC: 1646 AN: 57080

Other (OTH) AF: 0.126 AC: 228 AN: 1816

Alfa AF: 0.0788 Hom.: 231

Asia WGS AF: 0.413 AC: 1388 AN: 3374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	8.8
DANN	Benign	0.66
PhyloP100		0.077
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: rs12753710; hg19: chr1-169231542;