1-169132697-C-T

Variant names:

• chr1-169132697-C-T
• rs1138486
• NM_013330.5:c.*88G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013330.5(NME7):​c.*88G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,264,786 control chromosomes in the GnomAD database, including 16,621 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 0.13 (2554 hom., cov: 32)
  • Exomes 𝑓: 0.10 (14067 hom.)
• Consequence: NME7 NM_013330.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 16 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME7	NM_013330.5	c.*88G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000367811.8	NP_037462.1
ATP1B1	NM_001677.4	c.*1142C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000367815.9	NP_001668.1
NME7	NR_104229.2	n.1369G>A		non_coding_transcript_exon_variant	Exon 13 of 13
NME7	NM_197972.3	c.*88G>A		3_prime_UTR_variant	Exon 12 of 12		NP_932076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME7	ENST00000367811.8	c.*88G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_013330.5	ENSP00000356785.3
ATP1B1	ENST00000367815.9	c.*1142C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001677.4	ENSP00000356789.3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19587 AN: 152010 Hom.: 2550 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.100 AC: 111650 AN: 1112658 Hom.: 14067 Cov.: 14 AF XY: 0.102 AC XY: 57652 AN XY: 565322

African (AFR) AF: 0.168 AC: 4365 AN: 25968

American (AMR) AF: 0.157 AC: 6054 AN: 38560

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3333 AN: 21662

East Asian (EAS) AF: 0.695 AC: 25938 AN: 37344

South Asian (SAS) AF: 0.187 AC: 13300 AN: 71248

European-Finnish (FIN) AF: 0.0702 AC: 3588 AN: 51122

Middle Eastern (MID) AF: 0.139 AC: 694 AN: 5000

European-Non Finnish (NFE) AF: 0.0590 AC: 47968 AN: 813254

Other (OTH) AF: 0.132 AC: 6410 AN: 48500

GnomAD4 genome AF: 0.129 AC: 19634 AN: 152128 Hom.: 2554 Cov.: 32 AF XY: 0.135 AC XY: 10057 AN XY: 74366

African (AFR) AF: 0.165 AC: 6828 AN: 41492

American (AMR) AF: 0.138 AC: 2102 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3466

East Asian (EAS) AF: 0.733 AC: 3788 AN: 5168

South Asian (SAS) AF: 0.220 AC: 1058 AN: 4810

European-Finnish (FIN) AF: 0.0713 AC: 756 AN: 10604

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0620 AC: 4213 AN: 67996

Other (OTH) AF: 0.139 AC: 294 AN: 2110

Alfa AF: 0.0851 Hom.: 468

Bravo AF: 0.138

Asia WGS AF: 0.443 AC: 1536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		1.0
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: rs1138486; hg19: chr1-169101935;