3-131382247-C-A

Variant names:

• chr3-131382247-C-A
• rs2097456084
• NM_152395.3:c.340C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152395.3(NUDT16):​c.340C>A​(p.Arg114Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUDT16 NM_152395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.331

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03835419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT16	NM_152395.3	c.340C>A	p.Arg114Ser	missense_variant	Exon 2 of 3	ENST00000521288.2	NP_689608.2
NUDT16	NM_001171906.2	c.340C>A	p.Arg114Ser	missense_variant	Exon 2 of 2		NP_001165377.1
NUDT16	NM_001171905.2	c.202C>A	p.Arg68Ser	missense_variant	Exon 2 of 4		NP_001165376.1
NUDT16	NR_033268.2	n.474C>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.340C>A	p.Arg114Ser	missense_variant	Exon 2 of 3	1	NM_152395.3	ENSP00000429274.2
NUDT16	ENST00000502852.1	c.340C>A	p.Arg114Ser	missense_variant	Exon 2 of 2	2		ENSP00000422375.1
NUDT16	ENST00000537561.5	c.202C>A	p.Arg68Ser	missense_variant	Exon 2 of 4	5		ENSP00000440230.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.340C>A (p.R114S) alteration is located in exon 2 (coding exon 2) of the NUDT16 gene. This alteration results from a C to A substitution at nucleotide position 340, causing the arginine (R) at amino acid position 114 to be replaced by a serine (S). 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	0.24
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.014	.;T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.43	T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.038	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.066
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.045	.;B;.
Vest4		0.40
MutPred		0.30		.;Gain of glycosylation at T116 (P = 0.014);Gain of glycosylation at T116 (P = 0.014);
MVP		0.092
MPC		0.61
ClinPred		0.22	T
GERP RS		1.9
Varity_R		0.63
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2097456084; hg19: chr3-131101091;