3-131383324-A-T

Variant names:

• chr3-131383324-A-T
• NM_152395.3:c.571A>T

Variant summary

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

The NM_152395.3(NUDT16):​c.571A>T​(p.Ile191Phe) 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. 13/17 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: 0.0110

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=0.06765783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT16	NM_152395.3	c.571A>T	p.Ile191Phe	missense_variant	Exon 3 of 3	ENST00000521288.2	NP_689608.2
NUDT16	NM_001171905.2	c.382-20A>T		intron_variant	Intron 3 of 3		NP_001165376.1
NUDT16	NR_033268.2	n.705A>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT16	ENST00000521288.2	c.571A>T	p.Ile191Phe	missense_variant	Exon 3 of 3	1	NM_152395.3	ENSP00000429274.2
NUDT16	ENST00000502852.1	c.*733A>T		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000422375.1
NUDT16	ENST00000537561.5	c.382-20A>T		intron_variant	Intron 3 of 3	5		ENSP00000440230.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.571A>T (p.I191F) alteration is located in exon 3 (coding exon 3) of the NUDT16 gene. This alteration results from a A to T substitution at nucleotide position 571, causing the isoleucine (I) at amino acid position 191 to be replaced by a phenylalanine (F). 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	0.072
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.052
Sift	Benign	0.035	D
Sift4G	Uncertain	0.033	D
Polyphen		0.30	B
Vest4		0.078
MutPred		0.20		Gain of methylation at K190 (P = 0.0391);
MVP		0.067
ClinPred		0.12	T
GERP RS		0.41
Varity_R		0.15

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: chr3-131102168;