dbSNP rs14293: NME4:p.Ser120Ser (chr16-399659-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.16

Publications

17 publications found

Variant links:

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]

NME4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME4	NM_005009.3 link	c.360G>A	p.Ser120Ser	synonymous_variant	Exon 4 of 5	ENST00000219479.7	NP_005000.1	O00746-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME4	ENST00000219479.7 link	c.360G>A	p.Ser120Ser	synonymous_variant	Exon 4 of 5	1	NM_005009.3	ENSP00000219479.2		O00746-1

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

67982

AN:

151884

Hom.:

15716

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.410

AC XY:

297573

AN XY:

726624

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

19376

38752

58127

77503

96879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13984

27968

41952

55936

69920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.448

AC:

68073

AN:

152002

Hom.:

15753

Cov.:

AF XY:

0.450

AC XY:

33424

AN XY:

74308

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27059

AN:

67912

Other (OTH)

AF:

0.404

AC:

855

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1902

3803

5705

7606

9508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.83

PhyloP100

-3.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over