16-1770766-C-T

Variant names:

• chr16-1770766-C-T
• rs1183704486
• NM_002513.3:c.393G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

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

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 3880077.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.91 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME3	NM_002513.3	c.393G>A	p.Lys131Lys	splice_region_variant, synonymous_variant	Exon 5 of 5	ENST00000219302.8	NP_002504.2
NME3	XM_005255332.5	c.385G>A	p.Glu129Lys	missense_variant, splice_region_variant	Exon 5 of 5		XP_005255389.1
NME3	XM_011522504.3	c.404G>A	p.Arg135Lys	missense_variant, splice_region_variant	Exon 5 of 5		XP_011520806.1
NME3	XM_011522503.3	c.396G>A	p.Arg132Arg	splice_region_variant, synonymous_variant	Exon 5 of 5		XP_011520805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME3	ENST00000219302.8	c.393G>A	p.Lys131Lys	splice_region_variant, synonymous_variant	Exon 5 of 5	1	NM_002513.3	ENSP00000219302.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000882 AC: 2 AN: 226802 Hom.: 0 AF XY: 0.00000800 AC XY: 1 AN XY: 124962

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 SAS 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: 0.00000621 AC: 9 AN: 1449830 Hom.: 0 Cov.: 31 AF XY: 0.00000555 AC XY: 4 AN XY: 720460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000153

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 07, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.022	T
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.16	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.20	T
Sift4G	Benign	0.32	T
MVP		0.93
GERP RS		2.5

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

LitVar

Other links and lift over

dbSNP: rs1183704486; hg19: chr16-1820767;