1-169319532-T-C

Variant names:

• chr1-169319532-T-C
• rs10753786
• NM_013330.5:c.278+3585A>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.278+3585A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,910 control chromosomes in the GnomAD database, including 24,428 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 0.56 (24428 hom., cov: 31)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• Publications: 5 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]

NME7 Gene-Disease associations (from GenCC):

• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000235575 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.588 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.278+3585A>G		intron	N/A	NP_037462.1
	NME7	NM_197972.3		c.170+3585A>G		intron	N/A	NP_932076.1
	NME7	NR_104229.2		n.365+3585A>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.278+3585A>G		intron	N/A	ENSP00000356785.3
	NME7	ENST00000524967.5	TSL:1	n.340+3585A>G		intron	N/A
	NME7	ENST00000472647.5	TSL:2	c.170+3585A>G		intron	N/A	ENSP00000433341.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85461 AN: 151792 Hom.: 24388 Cov.: 31

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.563 AC: 85554 AN: 151910 Hom.: 24428 Cov.: 31 AF XY: 0.558 AC XY: 41409 AN XY: 74248

African (AFR) AF: 0.580 AC: 24043 AN: 41436

American (AMR) AF: 0.598 AC: 9130 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1909 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1345 AN: 5174

South Asian (SAS) AF: 0.342 AC: 1644 AN: 4804

European-Finnish (FIN) AF: 0.567 AC: 5977 AN: 10534

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39595 AN: 67910

Other (OTH) AF: 0.558 AC: 1176 AN: 2108

Alfa AF: 0.573 Hom.: 39321

Bravo AF: 0.571

Asia WGS AF: 0.316 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.55
PhyloP100		-2.6
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: rs10753786; hg19: chr1-169288770;