rs78056639

Variant names:

• chr21-29039046-T-G
• rs78056639
• NM_006447.3:c.753T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006447.3(USP16):​c.753T>G​(p.Leu251Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000674 in 1,560,918 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (5 hom.)
• Consequence: USP16 NM_006447.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.172
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 21-29039046-T-G is Benign according to our data. Variant chr21-29039046-T-G is described in ClinVar as Benign. ClinVar VariationId is 721047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.172 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP16	NM_006447.3	MANE Select	c.753T>G	p.Leu251Leu	synonymous	Exon 8 of 18	NP_006438.1	Q9Y5T5-1
	USP16	NM_001032410.2		c.753T>G	p.Leu251Leu	synonymous	Exon 9 of 19	NP_001027582.1	Q9Y5T5-1
	USP16	NM_001001992.2		c.750T>G	p.Leu250Leu	synonymous	Exon 8 of 18	NP_001001992.1	Q9Y5T5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP16	ENST00000399976.7	TSL:1 MANE Select	c.753T>G	p.Leu251Leu	synonymous	Exon 8 of 18	ENSP00000382858.2	Q9Y5T5-1
	USP16	ENST00000399975.7	TSL:1	c.750T>G	p.Leu250Leu	synonymous	Exon 8 of 18	ENSP00000382857.3	Q9Y5T5-2
	USP16	ENST00000474835.5	TSL:1	n.921T>G		non_coding_transcript_exon	Exon 8 of 17

Frequencies

GnomAD3 genomes AF: 0.00361 AC: 549 AN: 152132 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000833 AC: 184 AN: 220868 AF XY: 0.000665

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.000817

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.000391

GnomAD4 exome AF: 0.000357 AC: 503 AN: 1408668 Hom.: 5 Cov.: 30 AF XY: 0.000347 AC XY: 243 AN XY: 700724

African (AFR) AF: 0.0121 AC: 370 AN: 30670

American (AMR) AF: 0.00115 AC: 43 AN: 37374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24418

East Asian (EAS) AF: 0.00 AC: 0 AN: 37284

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51794

Middle Eastern (MID) AF: 0.00162 AC: 9 AN: 5572

European-Non Finnish (NFE) AF: 0.0000313 AC: 34 AN: 1085654

Other (OTH) AF: 0.000798 AC: 46 AN: 57662

GnomAD4 genome AF: 0.00361 AC: 549 AN: 152250 Hom.: 2 Cov.: 33 AF XY: 0.00343 AC XY: 255 AN XY: 74428

African (AFR) AF: 0.0122 AC: 507 AN: 41548

American (AMR) AF: 0.00203 AC: 31 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68016

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00150 Hom.: 1

Bravo AF: 0.00412

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.2
DANN	Benign	0.79
PhyloP100		0.17
Mutation Taster		=96/4	polymorphism

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: rs78056639; hg19: chr21-30411367;