chr1-169159913-T-C

Variant names:

• chr1-169159913-T-C
• rs12744184
• NM_013330.5:c.1098+9534A>G

Variant summary

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

The NM_013330.5(NME7):​c.1098+9534A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,918 control chromosomes in the GnomAD database, including 11,605 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 0.38 (11605 hom., cov: 31)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME7	NM_013330.5	MANE Select	c.1098+9534A>G		intron	N/A	NP_037462.1
	NME7	NM_197972.3		c.990+9534A>G		intron	N/A	NP_932076.1
	NME7	NR_104229.2		n.1248+9534A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME7	ENST00000367811.8	TSL:1 MANE Select	c.1098+9534A>G		intron	N/A	ENSP00000356785.3
	NME7	ENST00000472647.5	TSL:2	c.990+9534A>G		intron	N/A	ENSP00000433341.1
	NME7	ENST00000493481.1	TSL:5	n.137+9520A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58196 AN: 151798 Hom.: 11596 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.383 AC: 58243 AN: 151918 Hom.: 11605 Cov.: 31 AF XY: 0.384 AC XY: 28495 AN XY: 74240

African (AFR) AF: 0.320 AC: 13250 AN: 41408

American (AMR) AF: 0.351 AC: 5357 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1414 AN: 3462

East Asian (EAS) AF: 0.730 AC: 3768 AN: 5162

South Asian (SAS) AF: 0.327 AC: 1574 AN: 4816

European-Finnish (FIN) AF: 0.424 AC: 4478 AN: 10558

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 27000 AN: 67940

Other (OTH) AF: 0.395 AC: 835 AN: 2114

Alfa AF: 0.386 Hom.: 15008

Bravo AF: 0.380

Asia WGS AF: 0.495 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.52
PhyloP100		-0.65
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: rs12744184; hg19: chr1-169129151;