Genetic Variant NUDT16L1:p.Val125Met (chr16-4694197-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032349.4(NUDT16L1):c.373G>A(p.Val125Met) 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

NUDT16L1
NM_032349.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Publications

0 publications found

Variant links:

Genes affected

NUDT16L1 (HGNC:28154): (nudix hydrolase 16 like 1) Enables snoRNA binding activity. Involved in negative regulation of double-strand break repair via nonhomologous end joining. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NUDT16L1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12399304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUDT16L1	NM_032349.4	MANE Select	c.373G>A	p.Val125Met	missense	Exon 2 of 3	NP_115725.1	Q9BRJ7-1
NUDT16L1	NM_001370585.1		c.367G>A	p.Val123Met	missense	Exon 2 of 3	NP_001357514.1
NUDT16L1	NM_001193452.1		c.373G>A	p.Val125Met	missense	Exon 2 of 3	NP_001180381.1	W4VSQ8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUDT16L1	ENST00000304301.11	TSL:1 MANE Select	c.373G>A	p.Val125Met	missense	Exon 2 of 3	ENSP00000306670.5	Q9BRJ7-1
NUDT16L1	ENST00000405142.1	TSL:1	c.373G>A	p.Val125Met	missense	Exon 2 of 2	ENSP00000458144.1	Q9BRJ7-2
NUDT16L1	ENST00000860911.1		c.367G>A	p.Val123Met	missense	Exon 2 of 3	ENSP00000530970.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

161510

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1408130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698552

African (AFR)

AF:

0.00

AC:

AN:

30678

American (AMR)

AF:

0.00

AC:

AN:

39854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25124

East Asian (EAS)

AF:

0.00

AC:

AN:

36120

South Asian (SAS)

AF:

0.00

AC:

AN:

82080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094168

Other (OTH)

AF:

0.00

AC:

AN:

58676

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000873

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.029

Eigen_PC

Benign

-0.035

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.92

PhyloP100

1.5

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.2

REVEL

Benign

0.046

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.011

Polyphen

0.73

Vest4

0.57

MutPred

0.33

Gain of catalytic residue at V125 (P = 0.0748)

MVP

0.34

MPC

0.58

ClinPred

0.68

GERP RS

2.9

PromoterAI

0.086

Neutral

(source)

Varity_R

0.39

gMVP

0.62

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over