dbSNP rs141312121: USP16:p.Tyr295Ser (chr21-29039501-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006447.3(USP16):c.884A>C(p.Tyr295Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

USP16
NM_006447.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2278044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP16	NM_006447.3 link	c.884A>C	p.Tyr295Ser	missense_variant	Exon 9 of 18	ENST00000399976.7	NP_006438.1	Q9Y5T5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USP16	ENST00000399976.7 link	c.884A>C	p.Tyr295Ser	missense_variant	Exon 9 of 18	1	NM_006447.3	ENSP00000382858.2	Q9Y5T5-1
USP16	ENST00000399975.7 link	c.881A>C	p.Tyr294Ser	missense_variant	Exon 9 of 18	1		ENSP00000382857.3	Q9Y5T5-2
USP16	ENST00000474835.5 link	n.1052A>C		non_coding_transcript_exon_variant	Exon 9 of 17	1
USP16	ENST00000334352.8 link	c.884A>C	p.Tyr295Ser	missense_variant	Exon 10 of 19	5		ENSP00000334808.4	Q9Y5T5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251208

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460956

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726830

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.26

.;T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

T;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;L

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.1

D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.37

B;B;B

Vest4

0.45

MutPred

0.64

.;Gain of disorder (P = 0.0052);Gain of disorder (P = 0.0052);

MVP

0.41

MPC

0.13

ClinPred

0.77

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.77

gMVP

0.68

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over