Variant chr1-169287356-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013330.5(NME7):c.701C>T(p.Ala234Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,610,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NME7
NM_013330.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

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]

NME7 links:

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]

ATP1B1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NME7	NM_013330.5 linkuse as main transcript	c.701C>T	p.Ala234Val	missense_variant	7/12	ENST00000367811.8
NME7	NM_197972.3 linkuse as main transcript	c.593C>T	p.Ala198Val	missense_variant	7/12
NME7	NR_104229.2 linkuse as main transcript	n.788C>T		non_coding_transcript_exon_variant	7/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME7	ENST00000367811.8 linkuse as main transcript	c.701C>T	p.Ala234Val	missense_variant	7/12	1	NM_013330.5	P1	Q9Y5B8-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000960

AC:

AN:

1458116

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.701C>T (p.A234V) alteration is located in exon 7 (coding exon 7) of the NME7 gene. This alteration results from a C to T substitution at nucleotide position 701, causing the alanine (A) at amino acid position 234 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.7

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.7

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.054

T;T

Polyphen

1.0

.;D

Vest4

0.74

MVP

0.86

MPC

0.14

ClinPred

0.99

GERP RS

4.6

Varity_R

0.46

gMVP

0.71

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over