1-169362564-A-G

Variant names:

• chr1-169362564-A-G
• rs2176473
• NM_013330.5:c.3+5144T>C

Variant summary

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

The NM_013330.5(NME7):​c.3+5144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,042 control chromosomes in the GnomAD database, including 32,151 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 0.65 (32151 hom., cov: 32)
• Consequence: NME7 NM_013330.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 11 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME7	NM_013330.5	MANE Select	c.3+5144T>C		intron	N/A	NP_037462.1	Q9Y5B8-1
	NME7	NM_197972.3		c.-75+5144T>C		intron	N/A	NP_932076.1	Q9Y5B8-2
	NME7	NR_104229.2		n.90+5144T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME7	ENST00000367811.8	TSL:1 MANE Select	c.3+5144T>C		intron	N/A	ENSP00000356785.3	Q9Y5B8-1
	NME7	ENST00000524967.5	TSL:1	n.65+5144T>C		intron	N/A
	NME7	ENST00000961401.1		c.3+5144T>C		intron	N/A	ENSP00000631460.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98353 AN: 151924 Hom.: 32102 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.648 AC: 98468 AN: 152042 Hom.: 32151 Cov.: 32 AF XY: 0.651 AC XY: 48373 AN XY: 74354

African (AFR) AF: 0.635 AC: 26319 AN: 41438

American (AMR) AF: 0.703 AC: 10740 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2286 AN: 3472

East Asian (EAS) AF: 0.925 AC: 4785 AN: 5172

South Asian (SAS) AF: 0.497 AC: 2396 AN: 4820

European-Finnish (FIN) AF: 0.687 AC: 7258 AN: 10566

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42552 AN: 67970

Other (OTH) AF: 0.651 AC: 1373 AN: 2110

Alfa AF: 0.628 Hom.: 24217

Bravo AF: 0.656

Asia WGS AF: 0.687 AC: 2393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.76
DANN	Benign	0.50
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: rs2176473; hg19: chr1-169331802;