Genetic Variant NM_002513.3:c.112G>T (chr16-1771345-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002513.3(NME3):c.112G>T(p.Val38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,282 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V38M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NME3
NM_002513.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.467

Publications

1 publications found

Variant links:

Genes affected

NME3 (HGNC:7851): (NME/NM23 nucleoside diphosphate kinase 3) Predicted to enable nucleoside diphosphate kinase activity. Predicted to be involved in apoptotic process and nucleotide metabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NME3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002513.3. 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
	NME3	NM_002513.3	MANE Select	c.112G>T	p.Val38Leu	missense	Exon 2 of 5	NP_002504.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NME3	ENST00000219302.8	TSL:1 MANE Select	c.112G>T	p.Val38Leu	missense	Exon 2 of 5	ENSP00000219302.3	Q13232
NME3	ENST00000568561.5	TSL:1	n.88G>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000455271.1	H3BPD9
NME3	ENST00000563498.1	TSL:2	c.-141G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000455435.1	H3BPR2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000194

AC:

AN:

206040

AF XY:

0.00000882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1442282

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715874

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32916

American (AMR)

AF:

0.0000696

AC:

AN:

43128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25738

East Asian (EAS)

AF:

0.00

AC:

AN:

38668

South Asian (SAS)

AF:

0.00

AC:

AN:

83806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104162

Other (OTH)

AF:

0.00

AC:

AN:

59532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ExAC

AF:

0.00000854

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.047

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.75

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.75

MutationAssessor

Pathogenic

3.1

PhyloP100

0.47

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.22

Sift

Uncertain

0.014

Sift4G

Uncertain

0.0080

Polyphen

0.018

Vest4

0.23

MutPred

0.61

Loss of MoRF binding (P = 0.1039)

MVP

0.39

MPC

0.43

ClinPred

0.62

GERP RS

2.7

PromoterAI

-0.0049

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.90

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over