16-1770891-C-A

Variant names:

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

Variant summary

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

The NM_002513.3(NME3):​c.382G>T​(p.Glu128*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NME3 NM_002513.3 stop_gained
• 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 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.382G>T	p.Glu128*	stop_gained	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>T	p.Glu128*	stop_gained	Exon 4 of 5	ENSP00000219302.3	Q13232
	NME3	ENST00000568561.5	TSL:1	n.*216G>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000455271.1	H3BPD9
	NME3	ENST00000568561.5	TSL:1	n.*216G>T		3_prime_UTR	Exon 4 of 5	ENSP00000455271.1	H3BPD9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425694 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 704004

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0000121 AC: 1 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: 0.00 AC: 0 AN: 1089984

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	49
DANN	Uncertain	0.99
Eigen	Uncertain	0.28
Eigen_PC	Benign	-0.054
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		2.0
Vest4		0.90
GERP RS		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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;