Variant 21-29043492-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006447.3(USP16):c.1249G>A(p.Glu417Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000092 in 1,597,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

USP16
NM_006447.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26

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=0.25965643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP16	NM_006447.3 linkuse as main transcript	c.1249G>A	p.Glu417Lys	missense_variant	13/18	ENST00000399976.7	NP_006438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP16	ENST00000399976.7 linkuse as main transcript	c.1249G>A	p.Glu417Lys	missense_variant	13/18	1	NM_006447.3	ENSP00000382858	P5	Q9Y5T5-1
USP16	ENST00000399975.7 linkuse as main transcript	c.1246G>A	p.Glu416Lys	missense_variant	13/18	1		ENSP00000382857	A1	Q9Y5T5-2
USP16	ENST00000474835.5 linkuse as main transcript	n.2311G>A		non_coding_transcript_exon_variant	12/17	1
USP16	ENST00000334352.8 linkuse as main transcript	c.1249G>A	p.Glu417Lys	missense_variant	14/19	5		ENSP00000334808	P5	Q9Y5T5-1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000837

AC:

AN:

238858

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

129546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000131

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:

0.000127

Gnomad OTH exome

AF:

0.000354

GnomAD4 exome

AF:

0.0000830

AC:

120

AN:

1445096

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

718582

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000407

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000727

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000597

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.000177

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.1249G>A (p.E417K) alteration is located in exon 14 (coding exon 12) of the USP16 gene. This alteration results from a G to A substitution at nucleotide position 1249, causing the glutamic acid (E) at amino acid position 417 to be replaced by a lysine (K). 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

0.089

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.040

.;T;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

D;.;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.023

D;D;D

Sift4G

Benign

0.23

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.49

MVP

0.30

MPC

0.12

ClinPred

0.17

GERP RS

5.2

Varity_R

0.21

gMVP

0.38

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