Genetic Variant NUDT16L1:p.Arg55Cys (chr16-4693987-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_032349.4(NUDT16L1):c.163C>T(p.Arg55Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,425,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

NUDT16L1
NM_032349.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

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: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.955

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.163C>T	p.Arg55Cys	missense	Exon 2 of 3	NP_115725.1	Q9BRJ7-1
NUDT16L1	NM_001370585.1		c.157C>T	p.Arg53Cys	missense	Exon 2 of 3	NP_001357514.1
NUDT16L1	NM_001193452.1		c.163C>T	p.Arg55Cys	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.163C>T	p.Arg55Cys	missense	Exon 2 of 3	ENSP00000306670.5	Q9BRJ7-1
NUDT16L1	ENST00000405142.1	TSL:1	c.163C>T	p.Arg55Cys	missense	Exon 2 of 2	ENSP00000458144.1	Q9BRJ7-2
NUDT16L1	ENST00000860911.1		c.157C>T	p.Arg53Cys	missense	Exon 2 of 3	ENSP00000530970.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1425404

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

709282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29500

American (AMR)

AF:

0.00

AC:

AN:

41520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24914

East Asian (EAS)

AF:

0.00

AC:

AN:

35458

South Asian (SAS)

AF:

0.00

AC:

AN:

83176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.0000145

AC:

AN:

1100238

Other (OTH)

AF:

0.00

AC:

AN:

58976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

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

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.33

MetaRNN

Pathogenic

0.96

MetaSVM

Benign

-0.80

PhyloP100

4.2

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.53

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.91

MutPred

0.88

Loss of methylation at R55 (P = 0.0211)

MVP

0.49

MPC

1.4

ClinPred

1.0

GERP RS

4.3

PromoterAI

0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.88

gMVP

0.91

Mutation Taster

=23/77

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over