rs11658877

chr17-5169021-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001304284.2(USP6):c.3483C>T(p.Ser1161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,613,018 control chromosomes in the GnomAD database, including 287,873 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 0.48 (20200 hom., cov: 32)
  • Exomes 𝑓: 0.59 (267673 hom.)
• Consequence: USP6 NM_001304284.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

Genes affected

USP6 (HGNC:12629): (ubiquitin specific peptidase 6) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination and regulation of vesicle-mediated transport. Located in plasma membrane and recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.018 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP6	NM_001304284.2	c.3483C>T	p.Ser1161=	synonymous_variant	35/38	ENST00000574788.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP6	ENST00000574788.6	c.3483C>T	p.Ser1161=	synonymous_variant	35/38	1	NM_001304284.2	P1
USP6	ENST00000250066.6	c.3483C>T	p.Ser1161=	synonymous_variant	27/30	1		P1
USP6	ENST00000572949.5	c.*1010C>T		3_prime_UTR_variant, NMD_transcript_variant	26/29	2
USP6	ENST00000575709.5	c.*2563C>T		3_prime_UTR_variant, NMD_transcript_variant	28/31	2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72761 AN: 152010 Hom.: 20205 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.550

GnomAD3 exomes AF: 0.509 AC: 127189 AN: 250002 Hom.: 36329 AF XY: 0.508 AC XY: 68688 AN XY: 135102

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.562

Gnomad ASJ exome AF: 0.613

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.281

Gnomad FIN exome AF: 0.471

Gnomad NFE exome AF: 0.648

Gnomad OTH exome AF: 0.554

GnomAD4 exome AF: 0.590 AC: 861205 AN: 1460890 Hom.: 267673 Cov.: 71 AF XY: 0.582 AC XY: 422761 AN XY: 726712

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.622

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.488

Gnomad4 NFE exome AF: 0.648

Gnomad4 OTH exome AF: 0.549

GnomAD4 genome AF: 0.478 AC: 72767 AN: 152128 Hom.: 20200 Cov.: 32 AF XY: 0.466 AC XY: 34672 AN XY: 74370

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.544

Alfa AF: 0.602 Hom.: 9656

Bravo AF: 0.481

Asia WGS AF: 0.215 AC: 750 AN: 3478

EpiCase AF: 0.647

EpiControl AF: 0.645

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	3.6
Dann	Benign	0.38

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: rs11658877; hg19: chr17-5072316; COSMIC: COSV51474638;