rs14293

Positions:

• chr16-399659-G-A
• chr16-399659-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005009.3(NME4):​c.360G>A​(p.Ser120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,612,600 control chromosomes in the GnomAD database, including 138,648 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 0.45 (15753 hom., cov: 32)
  • Exomes 𝑓: 0.41 (122895 hom.)
• Consequence: NME4 NM_005009.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16

Genes affected

NME4 (HGNC:7852): (NME/NM23 nucleoside diphosphate kinase 4) The nucleoside diphosphate (NDP) kinases (EC 2.7.4.6) are ubiquitous enzymes that catalyze transfer of gamma-phosphates, via a phosphohistidine intermediate, between nucleoside and dioxynucleoside tri- and diphosphates. The enzymes are products of the nm23 gene family, which includes NME4 (Milon et al., 1997 [PubMed 9099850]).[supplied by OMIM, May 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-3.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NME4	NM_005009.3	c.360G>A	p.Ser120=	synonymous_variant	4/5	ENST00000219479.7	NP_005000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NME4	ENST00000219479.7	c.360G>A	p.Ser120=	synonymous_variant	4/5	1	NM_005009.3	ENSP00000219479	P2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67982 AN: 151884 Hom.: 15716 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.400

GnomAD3 exomes AF: 0.423 AC: 105963 AN: 250426 Hom.: 22860 AF XY: 0.422 AC XY: 57279 AN XY: 135680

Gnomad AFR exome AF: 0.564

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.365

Gnomad SAS exome AF: 0.470

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.397

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.408 AC: 596450 AN: 1460598 Hom.: 122895 Cov.: 46 AF XY: 0.410 AC XY: 297573 AN XY: 726624

Gnomad4 AFR exome AF: 0.570

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.340

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.448 AC: 68073 AN: 152002 Hom.: 15753 Cov.: 32 AF XY: 0.450 AC XY: 33424 AN XY: 74308

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.404

Alfa AF: 0.384 Hom.: 3943

Bravo AF: 0.447

Asia WGS AF: 0.414 AC: 1438 AN: 3478

EpiCase AF: 0.389

EpiControl AF: 0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs14293; hg19: chr16-449659; COSMIC: COSV54791127; COSMIC: COSV54791127;