chr16-399659-G-A

Variant names:

• chr16-399659-G-A
• rs14293
• NM_005009.3:c.360G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005009.3(NME4):​c.360G>A​(p.Ser120Ser) 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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.009).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005009.3. 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
	NME4	NM_005009.3	MANE Select	c.360G>A	p.Ser120Ser	synonymous	Exon 4 of 5	NP_005000.1
	NME4	NM_001286435.2		c.360G>A	p.Ser120Ser	synonymous	Exon 4 of 5	NP_001273364.1
	NME4	NM_001286433.2		c.258G>A	p.Ser86Ser	synonymous	Exon 3 of 4	NP_001273362.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME4	ENST00000219479.7	TSL:1 MANE Select	c.360G>A	p.Ser120Ser	synonymous	Exon 4 of 5	ENSP00000219479.2
	NME4	ENST00000382940.8	TSL:3	c.384G>A	p.Ser128Ser	synonymous	Exon 5 of 6	ENSP00000372398.4
	NME4	ENST00000433358.5	TSL:3	c.345G>A	p.Ser115Ser	synonymous	Exon 4 of 5	ENSP00000405925.1

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

GnomAD2 exomes AF: 0.423 AC: 105963 AN: 250426 AF XY: 0.422

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 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

African (AFR) AF: 0.570 AC: 19071 AN: 33478

American (AMR) AF: 0.444 AC: 19837 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 8883 AN: 26120

East Asian (EAS) AF: 0.370 AC: 14676 AN: 39694

South Asian (SAS) AF: 0.473 AC: 40775 AN: 86248

European-Finnish (FIN) AF: 0.440 AC: 23109 AN: 52570

Middle Eastern (MID) AF: 0.341 AC: 1965 AN: 5766

European-Non Finnish (NFE) AF: 0.399 AC: 443460 AN: 1111644

Other (OTH) AF: 0.409 AC: 24674 AN: 60370

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

African (AFR) AF: 0.562 AC: 23289 AN: 41438

American (AMR) AF: 0.421 AC: 6433 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1900 AN: 5168

South Asian (SAS) AF: 0.472 AC: 2274 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4794 AN: 10592

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27059 AN: 67912

Other (OTH) AF: 0.404 AC: 855 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.83
PhyloP100		-3.2
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: rs14293; hg19: chr16-449659; COSMIC: COSV54791127; COSMIC: COSV54791127;