17-5132426-G-C

Variant names:

• chr17-5132426-G-C
• rs145160344
• NM_001304284.2:c.186G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001304284.2(USP6):​c.186G>C​(p.Arg62Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,612,152 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (151 hom.)
• Consequence: USP6 NM_001304284.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0500
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-5132426-G-C is Benign according to our data. Variant chr17-5132426-G-C is described in ClinVar as Benign. ClinVar VariationId is 790879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.05 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00179 (272/152320) while in subpopulation SAS AF = 0.0547 (264/4828). AF 95% confidence interval is 0.0493. There are 4 homozygotes in GnomAd4. There are 199 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304284.2. 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.186G>C	p.Arg62Arg	synonymous	Exon 12 of 38	NP_001291213.1	P35125-1
	USP6	NM_004505.4		c.186G>C	p.Arg62Arg	synonymous	Exon 4 of 30	NP_004496.2	P35125-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP6	ENST00000574788.6	TSL:1 MANE Select	c.186G>C	p.Arg62Arg	synonymous	Exon 12 of 38	ENSP00000460380.1	P35125-1
	USP6	ENST00000250066.6	TSL:1	c.186G>C	p.Arg62Arg	synonymous	Exon 4 of 30	ENSP00000250066.6	P35125-1
	USP6	ENST00000357482.5	TSL:1	n.632G>C		non_coding_transcript_exon	Exon 5 of 8

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 272 AN: 152202 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00637 AC: 1597 AN: 250850 AF XY: 0.00865

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00315 AC: 4604 AN: 1459832 Hom.: 151 Cov.: 33 AF XY: 0.00457 AC XY: 3322 AN XY: 726230

African (AFR) AF: 0.0000898 AC: 3 AN: 33410

American (AMR) AF: 0.0000895 AC: 4 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0507 AC: 4368 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00164 AC: 7 AN: 4258

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111822

Other (OTH) AF: 0.00312 AC: 188 AN: 60216

GnomAD4 genome AF: 0.00179 AC: 272 AN: 152320 Hom.: 4 Cov.: 32 AF XY: 0.00267 AC XY: 199 AN XY: 74472

African (AFR) AF: 0.0000962 AC: 4 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0547 AC: 264 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000359

Asia WGS AF: 0.0220 AC: 76 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.7
DANN	Benign	0.35
PhyloP100		0.050
Mutation Taster		=299/1	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: rs145160344; hg19: chr17-5035721;