rs11658877

Variant names:

• chr17-5169021-C-T
• rs11658877
• NM_001304284.2:c.3483C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004505.4(USP6):​c.3483C>T​(p.Ser1161Ser) 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_004505.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004505.4. 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
	USP6	NM_001304284.2	MANE Select	c.3483C>T	p.Ser1161Ser	synonymous	Exon 35 of 38	NP_001291213.1
	USP6	NM_004505.4		c.3483C>T	p.Ser1161Ser	synonymous	Exon 27 of 30	NP_004496.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP6	ENST00000574788.6	TSL:1 MANE Select	c.3483C>T	p.Ser1161Ser	synonymous	Exon 35 of 38	ENSP00000460380.1
	USP6	ENST00000250066.6	TSL:1	c.3483C>T	p.Ser1161Ser	synonymous	Exon 27 of 30	ENSP00000250066.6
	USP6	ENST00000572949.5	TSL:2	n.*1010C>T		non_coding_transcript_exon	Exon 26 of 29	ENSP00000461581.1

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

GnomAD2 exomes AF: 0.509 AC: 127189 AN: 250002 AF XY: 0.508

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 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

African (AFR) AF: 0.202 AC: 6768 AN: 33454

American (AMR) AF: 0.565 AC: 25224 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 16224 AN: 26088

East Asian (EAS) AF: 0.134 AC: 5328 AN: 39694

South Asian (SAS) AF: 0.293 AC: 25209 AN: 86056

European-Finnish (FIN) AF: 0.488 AC: 26058 AN: 53394

Middle Eastern (MID) AF: 0.544 AC: 3124 AN: 5740

European-Non Finnish (NFE) AF: 0.648 AC: 720130 AN: 1111496

Other (OTH) AF: 0.549 AC: 33140 AN: 60338

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

African (AFR) AF: 0.223 AC: 9257 AN: 41514

American (AMR) AF: 0.580 AC: 8863 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3470

East Asian (EAS) AF: 0.158 AC: 819 AN: 5174

South Asian (SAS) AF: 0.278 AC: 1341 AN: 4818

European-Finnish (FIN) AF: 0.460 AC: 4863 AN: 10566

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.643 AC: 43713 AN: 67998

Other (OTH) AF: 0.544 AC: 1145 AN: 2104

Alfa AF: 0.591 Hom.: 10184

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.6
DANN	Benign	0.38
PhyloP100		-0.018
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: rs11658877; hg19: chr17-5072316; COSMIC: COSV51474638;