Genetic Variant NUDT16L1:p.Lys201Thr (chr16-4695145-A-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032349.4(NUDT16L1):c.602A>C(p.Lys201Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,074 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 6 hom. )

Consequence

NUDT16L1
NM_032349.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01125443).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT16L1	NM_032349.4 link	c.602A>C	p.Lys201Thr	missense_variant	Exon 3 of 3	ENST00000304301.11	NP_115725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT16L1	ENST00000304301.11 link	c.602A>C	p.Lys201Thr	missense_variant	Exon 3 of 3	1	NM_032349.4	ENSP00000306670.5		Q9BRJ7-1

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00106

AC:

265

AN:

250860

Hom.:

AF XY:

0.00110

AC XY:

149

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00158

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.00140

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00159

AC:

2317

AN:

1460972

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1097

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.000856

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.0000571

Gnomad4 NFE exome

AF:

0.00180

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00147

AC:

223

AN:

152102

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

109

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00175

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000879

Hom.:

Bravo

AF:

0.00152

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000980

AC:

119

EpiCase

AF:

0.00196

EpiControl

AF:

0.00148

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.602A>C (p.K201T) alteration is located in exon 3 (coding exon 3) of the NUDT16L1 gene. This alteration results from a A to C substitution at nucleotide position 602, causing the lysine (K) at amino acid position 201 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.80

N;.

REVEL

Benign

0.099

Sift

Benign

0.12

T;.

Sift4G

Benign

0.27

T;T

Polyphen

0.17

B;.

Vest4

0.46

MVP

0.31

MPC

0.68

ClinPred

0.026

GERP RS

4.4

Varity_R

0.27

gMVP

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over