chr16-1770891-C-G

Variant names:

• chr16-1770891-C-G
• rs371192760
• NM_002513.3:c.382G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002513.3(NME3):​c.382G>C​(p.Glu128Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. E128K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NME3 NM_002513.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22825316).

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.382G>C	p.Glu128Gln	missense	Exon 4 of 5	NP_002504.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME3	ENST00000219302.8	TSL:1 MANE Select	c.382G>C	p.Glu128Gln	missense	Exon 4 of 5	ENSP00000219302.3	Q13232
	NME3	ENST00000568561.5	TSL:1	n.*216G>C		non_coding_transcript_exon	Exon 4 of 5	ENSP00000455271.1	H3BPD9
	NME3	ENST00000568561.5	TSL:1	n.*216G>C		3_prime_UTR	Exon 4 of 5	ENSP00000455271.1	H3BPD9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425694 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 704004

African (AFR) AF: 0.00 AC: 0 AN: 32762

American (AMR) AF: 0.00 AC: 0 AN: 42098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24418

East Asian (EAS) AF: 0.00 AC: 0 AN: 39088

South Asian (SAS) AF: 0.00 AC: 0 AN: 82428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1089984

Other (OTH) AF: 0.00 AC: 0 AN: 58772

GnomAD4 genome Cov.: 34

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Benign	0.59
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.30	N
PhyloP100		2.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.33	N
REVEL	Uncertain	0.31
Sift	Benign	1.0	T
Sift4G	Benign	0.86	T
Polyphen		1.0	D
Vest4		0.34
MutPred		0.33		Gain of ubiquitination at K131 (P = 0.123)
MVP		0.86
MPC		1.1
ClinPred		0.50	T
GERP RS		0.79
Varity_R		0.55
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs371192760; hg19: chr16-1820892;