Variant 21-29040668-A-T 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.1011A>T(p.Glu337Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,387,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

USP16
NM_006447.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

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=0.10078353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP16	NM_006447.3 linkuse as main transcript	c.1011A>T	p.Glu337Asp	missense_variant	10/18	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.1011A>T	p.Glu337Asp	missense_variant	10/18	1	NM_006447.3	ENSP00000382858	P5	Q9Y5T5-1
USP16	ENST00000399975.7 linkuse as main transcript	c.1008A>T	p.Glu336Asp	missense_variant	10/18	1		ENSP00000382857	A1	Q9Y5T5-2
USP16	ENST00000474835.5 linkuse as main transcript	n.1179A>T		non_coding_transcript_exon_variant	10/17	1
USP16	ENST00000334352.8 linkuse as main transcript	c.1011A>T	p.Glu337Asp	missense_variant	11/19	5		ENSP00000334808	P5	Q9Y5T5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

236714

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000175

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:

0.00000288

AC:

AN:

1387216

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

692536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000105

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

Cov.:

ExAC

AF:

0.00000825

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

Mar 19, 2024

The c.1011A>T (p.E337D) alteration is located in exon 11 (coding exon 9) of the USP16 gene. This alteration results from a A to T substitution at nucleotide position 1011, causing the glutamic acid (E) at amino acid position 337 to be replaced by an aspartic acid (D). 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

0.095

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

.;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.042

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.76

T;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.0

.;L;L

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.045

D;D;D

Sift4G

Benign

0.17

T;T;T

Polyphen

0.23

B;B;B

Vest4

0.32

MutPred

0.37

.;Gain of ubiquitination at K339 (P = 0.1128);Gain of ubiquitination at K339 (P = 0.1128);

MVP

0.32

MPC

0.11

ClinPred

0.20

GERP RS

2.9

Varity_R

0.11

gMVP

0.34

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