3-131381811-G-A

Variant names:

• chr3-131381811-G-A
• rs763295353
• NM_152395.3:c.7G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152395.3(NUDT16):​c.7G>A​(p.Gly3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000834 in 1,558,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: NUDT16 NM_152395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

Genes affected

NUDT16 (HGNC:26442): (nudix hydrolase 16) Enables several functions, including RNA binding activity; metal ion binding activity; and purine ribonucleoside triphosphate binding activity. Involved in IDP catabolic process; RNA metabolic process; and positive regulation of cell cycle process. Located in cytoplasm; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NUDT16-DT (HGNC:27947): (NUDT16 divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076488614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT16	NM_152395.3	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 3	ENST00000521288.2	NP_689608.2
NUDT16	NM_001171906.2	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 2		NP_001165377.1
NUDT16	NM_001171905.2	c.-1+66G>A		intron_variant	Intron 1 of 3		NP_001165376.1
NUDT16	NR_033268.2	n.38G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT16	ENST00000521288.2	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 3	1	NM_152395.3	ENSP00000429274.2
NUDT16	ENST00000502852.1	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 2	2		ENSP00000422375.1
NUDT16	ENST00000537561.5	c.-1+66G>A		intron_variant	Intron 1 of 3	5		ENSP00000440230.1
NUDT16-DT	ENST00000660567.1	n.-155C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000782 AC: 11 AN: 1406360 Hom.: 0 Cov.: 31 AF XY: 0.00000574 AC XY: 4 AN XY: 696690

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7G>A (p.G3R) alteration is located in exon 1 (coding exon 1) of the NUDT16 gene. This alteration results from a G to A substitution at nucleotide position 7, causing the glycine (G) at amino acid position 3 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.0024	T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.016
Sift	Benign	0.30	T;T
Sift4G	Benign	0.58	T;T
Vest4		0.12
MutPred		0.18		Gain of MoRF binding (P = 0.0068);Gain of MoRF binding (P = 0.0068);
MVP		0.22
MPC		0.51
ClinPred		0.16	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.074
gMVP		0.76

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

Other links and lift over

dbSNP: rs763295353; hg19: chr3-131100655;