3-131381817-C-T

Variant names:

• chr3-131381817-C-T
• rs576393185
• NM_152395.3:c.13C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152395.3(NUDT16):​c.13C>T​(p.Arg5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUDT16 NM_152395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.139

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2646801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT16	NM_152395.3	c.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 3	ENST00000521288.2	NP_689608.2
NUDT16	NM_001171906.2	c.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 2		NP_001165377.1
NUDT16	NM_001171905.2	c.-1+72C>T		intron_variant	Intron 1 of 3		NP_001165376.1
NUDT16	NR_033268.2	n.44C>T		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.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 3	1	NM_152395.3	ENSP00000429274.2
NUDT16	ENST00000502852.1	c.13C>T	p.Arg5Cys	missense_variant	Exon 1 of 2	2		ENSP00000422375.1
NUDT16	ENST00000537561.5	c.-1+72C>T		intron_variant	Intron 1 of 3	5		ENSP00000440230.1
NUDT16-DT	ENST00000660567.1	n.-161G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1413666 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 701068

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.13C>T (p.R5C) alteration is located in exon 1 (coding exon 1) of the NUDT16 gene. This alteration results from a C to T substitution at nucleotide position 13, causing the arginine (R) at amino acid position 5 to be replaced by a cysteine (C). 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	0.26
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0070	D;D
Vest4		0.43
MutPred		0.26		Loss of disorder (P = 0.017);Loss of disorder (P = 0.017);
MVP		0.24
MPC		0.58
ClinPred		0.96	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.63
gMVP		0.89

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: rs576393185; hg19: chr3-131100661;