Genetic Variant NM_002513.3:c.393G>A (chr16-1770766-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_002513.3(NME3):c.393G>A(p.Lys131Lys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,449,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NME3
NM_002513.3 splice_region, synonymous

Scores

Splicing: ADA: 0.7044

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.91

Publications

0 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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19542664).

BP6

Variant 16-1770766-C-T is Benign according to our data. Variant chr16-1770766-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3880077.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.91 with no splicing effect.

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.393G>A	p.Lys131Lys	splice_region synonymous	Exon 5 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.393G>A	p.Lys131Lys	splice_region synonymous	Exon 5 of 5	ENSP00000219302.3	Q13232
NME3	ENST00000568561.5	TSL:1	n.*227G>A		splice_region non_coding_transcript_exon	Exon 5 of 5	ENSP00000455271.1	H3BPD9
NME3	ENST00000568561.5	TSL:1	n.*227G>A		3_prime_UTR	Exon 5 of 5	ENSP00000455271.1	H3BPD9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000882

AC:

AN:

226802

AF XY:

0.00000800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000116

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000621

AC:

AN:

1449830

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

720460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33274

American (AMR)

AF:

0.00

AC:

AN:

43794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25840

East Asian (EAS)

AF:

0.000153

AC:

AN:

39234

South Asian (SAS)

AF:

0.00

AC:

AN:

85426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1106930

Other (OTH)

AF:

0.00

AC:

AN:

59818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

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.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.022

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.16

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.20

PhyloP100

1.9

Sift4G

Benign

0.32

MVP

0.93

GERP RS

2.5

Mutation Taster

=49/51

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.70

dbscSNV1_RF

Benign

0.43

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