Genetic Variant NM_152395.3:c.408+179G>A (chr3-131382494-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_152395.3(NUDT16):c.408+179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00763 in 1,536,168 control chromosomes in the GnomAD database, including 722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 404 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 318 hom. )

Consequence

NUDT16
NM_152395.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0390

Publications

3 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.189976).

BP6

Variant 3-131382494-G-A is Benign according to our data. Variant chr3-131382494-G-A is described in ClinVar as Benign. ClinVar VariationId is 770147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152395.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUDT16	NM_152395.3	MANE Select	c.408+179G>A		intron	N/A	NP_689608.2	Q96DE0-1
NUDT16	NM_001171906.2		c.587G>A	p.Trp196*	stop_gained	Exon 2 of 2	NP_001165377.1	Q96DE0-4
NUDT16	NM_001171905.2		c.270+179G>A		intron	N/A	NP_001165376.1	Q96DE0-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUDT16	ENST00000521288.2	TSL:1 MANE Select	c.408+179G>A		intron	N/A	ENSP00000429274.2	Q96DE0-1
NUDT16	ENST00000502852.1	TSL:2	c.587G>A	p.Trp196*	stop_gained	Exon 2 of 2	ENSP00000422375.1	Q96DE0-4
NUDT16	ENST00000537561.5	TSL:5	c.270+179G>A		intron	N/A	ENSP00000440230.1	Q96DE0-3

Frequencies

GnomAD3 genomes

AF:

0.0392

AC:

5959

AN:

152140

Hom.:

404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0277

GnomAD2 exomes

AF:

0.00794

AC:

1072

AN:

135006

AF XY:

0.00617

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.00735

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000452

Gnomad OTH exome

AF:

0.00434

GnomAD4 exome

AF:

0.00416

AC:

5752

AN:

1383910

Hom.:

318

Cov.:

AF XY:

0.00361

AC XY:

2463

AN XY:

682918

show subpopulations

African (AFR)

AF:

0.139

AC:

4383

AN:

31592

American (AMR)

AF:

0.00860

AC:

307

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.000341

AC:

AN:

79254

European-Finnish (FIN)

AF:

0.000501

AC:

AN:

33950

Middle Eastern (MID)

AF:

0.00509

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.000415

AC:

448

AN:

1078888

Other (OTH)

AF:

0.00934

AC:

541

AN:

57912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

301

602

903

1204

1505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<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

AF:

0.0392

AC:

5974

AN:

152258

Hom.:

404

Cov.:

AF XY:

0.0372

AC XY:

2771

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.136

AC:

5666

AN:

41534

American (AMR)

AF:

0.0139

AC:

212

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68026

Other (OTH)

AF:

0.0274

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

258

516

773

1031

1289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0257

Hom.:

249

Bravo

AF:

0.0441

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.00440

AC:

214

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

0.070

CADD

Benign

5.5

(source)

DANN

Benign

0.72

Eigen

Benign

0.054

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.0074

PhyloP100

0.039

Vest4

0.024

GERP RS

0.20

Mutation Taster

=192/8

polymorphism (auto)

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over