Genetic Variant NM_001304284.2:c.3483C>T (chr17-5169021-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001304284.2(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_001304284.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0180

Publications

18 publications found

Variant links:

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]

USP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP6	NM_001304284.2 link	c.3483C>T	p.Ser1161Ser	synonymous_variant	Exon 35 of 38	ENST00000574788.6	NP_001291213.1	P35125-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP6	ENST00000574788.6 link	c.3483C>T	p.Ser1161Ser	synonymous_variant	Exon 35 of 38	1	NM_001304284.2	ENSP00000460380.1		P35125-1

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72761

AN:

152010

Hom.:

20205

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.582

AC XY:

422761

AN XY:

726712

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

19284

38567

57851

77134

96418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18456

36912

55368

73824

92280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.478

AC:

72767

AN:

152128

Hom.:

20200

Cov.:

AF XY:

0.466

AC XY:

34672

AN XY:

74370

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1684

3368

5051

6735

8419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.6

(source)

DANN

Benign

0.38

PhyloP100

-0.018

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over