chr3-131381841-C-A

Variant names:

• chr3-131381841-C-A
• rs1175507538
• NM_152395.3:c.37C>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.37C>A​(p.Leu13Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,440,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: NUDT16 NM_152395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.290

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=0.10050577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT16	NM_152395.3	c.37C>A	p.Leu13Met	missense_variant	Exon 1 of 3	ENST00000521288.2	NP_689608.2
NUDT16	NM_001171906.2	c.37C>A	p.Leu13Met	missense_variant	Exon 1 of 2		NP_001165377.1
NUDT16	NM_001171905.2	c.-1+96C>A		intron_variant	Intron 1 of 3		NP_001165376.1
NUDT16	NR_033268.2	n.68C>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.37C>A	p.Leu13Met	missense_variant	Exon 1 of 3	1	NM_152395.3	ENSP00000429274.2
NUDT16	ENST00000502852.1	c.37C>A	p.Leu13Met	missense_variant	Exon 1 of 2	2		ENSP00000422375.1
NUDT16	ENST00000537561.5	c.-1+96C>A		intron_variant	Intron 1 of 3	5		ENSP00000440230.1
NUDT16-DT	ENST00000660567.1	n.-185G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000160 AC: 23 AN: 1440234 Hom.: 0 Cov.: 31 AF XY: 0.0000126 AC XY: 9 AN XY: 716218

Gnomad4 AFR exome AF: 0.000453

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: 0.000134

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37C>A (p.L13M) alteration is located in exon 1 (coding exon 1) of the NUDT16 gene. This alteration results from a C to A substitution at nucleotide position 37, causing the leucine (L) at amino acid position 13 to be replaced by a methionine (M). 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	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.1
DANN	Benign	0.76
DEOGEN2	Benign	0.0096	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.024
Sift	Benign	0.34	T;T
Sift4G	Benign	0.27	T;T
Vest4		0.18
MutPred		0.32		Loss of glycosylation at S17 (P = 0.0459);Loss of glycosylation at S17 (P = 0.0459);
MVP		0.10
MPC		0.41
ClinPred		0.11	T
GERP RS		0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.23
gMVP		0.69

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: rs1175507538; hg19: chr3-131100685;