Genetic Variant USP16:p.Asp240Val (chr21-29038417-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006447.3(USP16):c.719A>T(p.Asp240Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000726 in 1,611,766 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

USP16
NM_006447.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.57

Publications

1 publications found

Variant links:

Genes affected

USP16 (HGNC:12614): (ubiquitin specific peptidase 16) This gene encodes a deubiquitinating enzyme that is phosphorylated at the onset of mitosis and then dephosphorylated at the metaphase/anaphase transition. It can deubiquitinate H2A, one of two major ubiquitinated proteins of chromatin, in vitro and a mutant form of the protein was shown to block cell division. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

USP16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.084685504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006447.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP16	NM_006447.3	MANE Select	c.719A>T	p.Asp240Val	missense	Exon 7 of 18	NP_006438.1	Q9Y5T5-1
USP16	NM_001032410.2		c.719A>T	p.Asp240Val	missense	Exon 8 of 19	NP_001027582.1	Q9Y5T5-1
USP16	NM_001001992.2		c.716A>T	p.Asp239Val	missense	Exon 7 of 18	NP_001001992.1	Q9Y5T5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP16	ENST00000399976.7	TSL:1 MANE Select	c.719A>T	p.Asp240Val	missense	Exon 7 of 18	ENSP00000382858.2	Q9Y5T5-1
USP16	ENST00000399975.7	TSL:1	c.716A>T	p.Asp239Val	missense	Exon 7 of 18	ENSP00000382857.3	Q9Y5T5-2
USP16	ENST00000474835.5	TSL:1	n.887A>T		non_coding_transcript_exon	Exon 7 of 17

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000876

AC:

AN:

251034

AF XY:

0.0000590

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0000870

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:

0.000163

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1459580

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

726216

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

33444

American (AMR)

AF:

0.0000671

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

86104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110322

Other (OTH)

AF:

0.000133

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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

AF:

0.000427

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00157

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000756

Hom.:

Bravo

AF:

0.000461

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

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

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.013

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

PhyloP100

6.6

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.2

REVEL

Benign

0.21

Sift

Benign

0.043

Sift4G

Benign

0.25

Polyphen

0.96

Vest4

0.45

MVP

0.48

MPC

0.52

ClinPred

0.076

GERP RS

4.9

Varity_R

0.18

gMVP

0.34

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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