Variant chr21-29037330-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000399976.7(USP16):c.503G>A(p.Ser168Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000349 in 1,430,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

USP16
ENST00000399976.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.270

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047422856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP16	NM_006447.3 linkuse as main transcript	c.503G>A	p.Ser168Asn	missense_variant	6/18	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.503G>A	p.Ser168Asn	missense_variant	6/18	1	NM_006447.3	ENSP00000382858	P5	Q9Y5T5-1
USP16	ENST00000399975.7 linkuse as main transcript	c.500G>A	p.Ser167Asn	missense_variant	6/18	1		ENSP00000382857	A1	Q9Y5T5-2
USP16	ENST00000474835.5 linkuse as main transcript	n.671G>A		non_coding_transcript_exon_variant	6/17	1
USP16	ENST00000334352.8 linkuse as main transcript	c.503G>A	p.Ser168Asn	missense_variant	7/19	5		ENSP00000334808	P5	Q9Y5T5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000349

AC:

AN:

1430930

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000457

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 06, 2021

The c.503G>A (p.S168N) alteration is located in exon 7 (coding exon 5) of the USP16 gene. This alteration results from a G to A substitution at nucleotide position 503, causing the serine (S) at amino acid position 168 to be replaced by an asparagine (N). 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

0.061

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.053

.;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.0095

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.70

T;.;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

.;N;N

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.32

B;B;B

Vest4

0.077

MutPred

0.24

.;Loss of phosphorylation at S168 (P = 0.0035);Loss of phosphorylation at S168 (P = 0.0035);

MVP

0.26

MPC

0.073

ClinPred

0.21

GERP RS

5.0

Varity_R

0.042

gMVP

0.24

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over