3-131381836-A-G

Variant names:

• chr3-131381836-A-G
• NM_152395.3:c.32A>G

Variant summary

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

The NM_152395.3(NUDT16):​c.32A>G​(p.Glu11Gly) 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)
• Consequence: NUDT16 NM_152395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

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=0.34694067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT16	NM_152395.3	c.32A>G	p.Glu11Gly	missense_variant	Exon 1 of 3	ENST00000521288.2	NP_689608.2
NUDT16	NM_001171906.2	c.32A>G	p.Glu11Gly	missense_variant	Exon 1 of 2		NP_001165377.1
NUDT16	NM_001171905.2	c.-1+91A>G		intron_variant	Intron 1 of 3		NP_001165376.1
NUDT16	NR_033268.2	n.63A>G		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.32A>G	p.Glu11Gly	missense_variant	Exon 1 of 3	1	NM_152395.3	ENSP00000429274.2
NUDT16	ENST00000502852.1	c.32A>G	p.Glu11Gly	missense_variant	Exon 1 of 2	2		ENSP00000422375.1
NUDT16	ENST00000537561.5	c.-1+91A>G		intron_variant	Intron 1 of 3	5		ENSP00000440230.1
NUDT16-DT	ENST00000660567.1	n.-180T>C		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.32A>G (p.E11G) alteration is located in exon 1 (coding exon 1) of the NUDT16 gene. This alteration results from a A to G substitution at nucleotide position 32, causing the glutamic acid (E) at amino acid position 11 to be replaced by a glycine (G). 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	0.20
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.013	D;D
Vest4		0.23
MutPred		0.35		Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);
MVP		0.26
MPC		0.50
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.90
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-131100680;