rs3766077

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013330.5(NME7):​c.990+19654T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,816 control chromosomes in the GnomAD database, including 7,735 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 0.31 ( 7735 hom., cov: 31)

Consequence

NME7
NM_013330.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.212
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NME7NM_013330.5 linkuse as main transcriptc.990+19654T>C intron_variant ENST00000367811.8
NME7NM_197972.3 linkuse as main transcriptc.882+19654T>C intron_variant
NME7NR_104229.2 linkuse as main transcriptn.1077+19654T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NME7ENST00000367811.8 linkuse as main transcriptc.990+19654T>C intron_variant 1 NM_013330.5 P1Q9Y5B8-1

Frequencies

GnomAD3 genomes
AF:
0.307
AC:
46559
AN:
151698
Hom.:
7729
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.207
Gnomad AMI
AF:
0.523
Gnomad AMR
AF:
0.261
Gnomad ASJ
AF:
0.380
Gnomad EAS
AF:
0.121
Gnomad SAS
AF:
0.183
Gnomad FIN
AF:
0.360
Gnomad MID
AF:
0.306
Gnomad NFE
AF:
0.386
Gnomad OTH
AF:
0.315
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.307
AC:
46582
AN:
151816
Hom.:
7735
Cov.:
31
AF XY:
0.301
AC XY:
22315
AN XY:
74216
show subpopulations
Gnomad4 AFR
AF:
0.208
Gnomad4 AMR
AF:
0.260
Gnomad4 ASJ
AF:
0.380
Gnomad4 EAS
AF:
0.121
Gnomad4 SAS
AF:
0.184
Gnomad4 FIN
AF:
0.360
Gnomad4 NFE
AF:
0.386
Gnomad4 OTH
AF:
0.313
Alfa
AF:
0.347
Hom.:
6047
Bravo
AF:
0.297
Asia WGS
AF:
0.147
AC:
512
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
2.0
DANN
Benign
0.78

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3766077; hg19: chr1-169180302; API