21-29029703-A-G

Variant names:

• chr21-29029703-A-G
• rs6516887
• NM_006447.3:c.62-892A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006447.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP16	NM_006447.3	MANE Select	c.62-892A>G		intron	N/A	NP_006438.1
	USP16	NM_001032410.2		c.62-892A>G		intron	N/A	NP_001027582.1
	USP16	NM_001001992.2		c.62-892A>G		intron	N/A	NP_001001992.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP16	ENST00000399976.7	TSL:1 MANE Select	c.62-892A>G		intron	N/A	ENSP00000382858.2
	USP16	ENST00000399975.7	TSL:1	c.62-892A>G		intron	N/A	ENSP00000382857.3
	USP16	ENST00000474835.5	TSL:1	n.230-892A>G		intron	N/A

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

African (AFR) AF: 0.325 AC: 13481 AN: 41432

American (AMR) AF: 0.164 AC: 2505 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3466

East Asian (EAS) AF: 0.147 AC: 758 AN: 5168

South Asian (SAS) AF: 0.118 AC: 570 AN: 4826

European-Finnish (FIN) AF: 0.0603 AC: 639 AN: 10600

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7003 AN: 67994

Other (OTH) AF: 0.158 AC: 333 AN: 2108

Alfa AF: 0.116 Hom.: 917

Bravo AF: 0.184

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.65
DANN	Benign	0.72
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6516887; hg19: chr21-30402024;