NM_013330.5:c.990+23057C>T

Variant names:

• chr1-169207661-G-A
• rs3753298
• NM_013330.5:c.990+23057C>T

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+23057C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 152,128 control chromosomes in the GnomAD database, including 227 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 0.048 (227 hom., cov: 32)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME7	NM_013330.5	c.990+23057C>T		intron_variant	Intron 10 of 11	ENST00000367811.8	NP_037462.1
NME7	NM_197972.3	c.882+23057C>T		intron_variant	Intron 10 of 11		NP_932076.1
NME7	NR_104229.2	n.1078-16956C>T		intron_variant	Intron 10 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME7	ENST00000367811.8	c.990+23057C>T		intron_variant	Intron 10 of 11	1	NM_013330.5	ENSP00000356785.3

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7232 AN: 152010 Hom.: 226 Cov.: 32

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0798

Gnomad FIN AF: 0.00510

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0440

Gnomad OTH AF: 0.0516

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

GnomAD4 genome AF: 0.0476 AC: 7245 AN: 152128 Hom.: 227 Cov.: 32 AF XY: 0.0477 AC XY: 3550 AN XY: 74384

African (AFR) AF: 0.0462 AC: 1919 AN: 41502

American (AMR) AF: 0.0477 AC: 728 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3472

East Asian (EAS) AF: 0.120 AC: 617 AN: 5160

South Asian (SAS) AF: 0.0803 AC: 387 AN: 4820

European-Finnish (FIN) AF: 0.00510 AC: 54 AN: 10596

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0440 AC: 2991 AN: 67992

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0405 Hom.: 11

Bravo AF: 0.0504

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.34
PhyloP100		-0.64
Mutation Taster		=99/1	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: rs3753298; hg19: chr1-169176899;