Genetic Variant NME3:p.Trp159* (chr16-1770682-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_002513.3(NME3):c.477G>A(p.Trp159*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,585,102 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0023 ( 8 hom. )

Consequence

NME3
NM_002513.3 stop_gained

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 16-1770682-C-T is Benign according to our data. Variant chr16-1770682-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3352216.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME3	NM_002513.3 link	c.477G>A	p.Trp159*	stop_gained	Exon 5 of 5	ENST00000219302.8	NP_002504.2	Q13232
NME3	XM_011522503.3 link	c.480G>A	p.Trp160*	stop_gained	Exon 5 of 5		XP_011520805.1
NME3	XM_005255332.5 link	c.469G>A	p.Gly157Arg	missense_variant	Exon 5 of 5		XP_005255389.1
NME3	XM_011522504.3 link	c.*77G>A		3_prime_UTR_variant	Exon 5 of 5		XP_011520806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME3	ENST00000219302.8 link	c.477G>A	p.Trp159*	stop_gained	Exon 5 of 5	1	NM_002513.3	ENSP00000219302.3		Q13232

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

217

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000969

AC:

192

AN:

198226

Hom.:

AF XY:

0.00105

AC XY:

113

AN XY:

107932

show subpopulations

Gnomad AFR exome

AF:

0.000842

Gnomad AMR exome

AF:

0.000646

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000358

Gnomad NFE exome

AF:

0.00181

Gnomad OTH exome

AF:

0.000586

GnomAD4 exome

AF:

0.00228

AC:

3261

AN:

1432726

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1544

AN XY:

710334

show subpopulations

Gnomad4 AFR exome

AF:

0.000395

Gnomad4 AMR exome

AF:

0.000564

Gnomad4 ASJ exome

AF:

0.0000781

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.000447

Gnomad4 NFE exome

AF:

0.00281

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00142

AC:

217

AN:

152376

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00134

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00115

AC:

ESP6500EA

AF:

0.00268

AC:

ExAC

AF:

0.000751

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NME3-related condition

Benign:1

Aug 20, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.47

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.92

Vest4

0.74

GERP RS

3.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over