rs6516887

chr21-29029703-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006447.3(USP16):c.62-892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,082 control chromosomes in the GnomAD database, including 2,931 homozygotes. 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 0.17 (2931 hom., cov: 32)
• Consequence: USP16 NM_006447.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP16	NM_006447.3	c.62-892A>G		intron_variant		ENST00000399976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP16	ENST00000399976.7	c.62-892A>G		intron_variant		1	NM_006447.3	P5

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25787 AN: 151964 Hom.: 2933 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.157

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.170 AC: 25814 AN: 152082 Hom.: 2931 Cov.: 32 AF XY: 0.166 AC XY: 12327 AN XY: 74364

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.158

Alfa AF: 0.117 Hom.: 717

Bravo AF: 0.184

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.65
Dann	Benign	0.72

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

Other links and lift over

dbSNP: rs6516887; hg19: chr21-30402024;