Variant rs11136254 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030974.4(SHARPIN):c.154C>A(p.Arg52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,531,066 control chromosomes in the GnomAD database, including 637,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 57704 hom., cov: 35)

Exomes 𝑓: 0.92 ( 579581 hom. )

Consequence

SHARPIN
NM_030974.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.788

Variant links:

Genes affected

SHARPIN (HGNC:25321): (SHANK associated RH domain interactor) Enables polyubiquitin modification-dependent protein binding activity. Involved in protein linear polyubiquitination and regulation of signal transduction. Located in cytosol. Part of LUBAC complex. [provided by Alliance of Genome Resources, Apr 2022]

SHARPIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 8-144103600-G-T is Benign according to our data. Variant chr8-144103600-G-T is described in ClinVar as [Benign]. Clinvar id is 403434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.788 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHARPIN	NM_030974.4 linkuse as main transcript	c.154C>A	p.Arg52=	synonymous_variant	1/9	ENST00000398712.7	NP_112236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHARPIN	ENST00000398712.7 linkuse as main transcript	c.154C>A	p.Arg52=	synonymous_variant	1/9	1	NM_030974.4	ENSP00000381698	P1	Q9H0F6-1

Frequencies

GnomAD3 genomes

AF:

0.865

AC:

131569

AN:

152120

Hom.:

57681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.709

Gnomad AMI

AF:

0.942

Gnomad AMR

AF:

0.912

Gnomad ASJ

AF:

0.922

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.959

Gnomad FIN

AF:

0.928

Gnomad MID

AF:

0.882

Gnomad NFE

AF:

0.918

Gnomad OTH

AF:

0.878

GnomAD3 exomes

AF:

0.927

AC:

117876

AN:

127126

Hom.:

54829

AF XY:

0.930

AC XY:

64811

AN XY:

69688

show subpopulations

Gnomad AFR exome

AF:

0.719

Gnomad AMR exome

AF:

0.944

Gnomad ASJ exome

AF:

0.926

Gnomad EAS exome

AF:

0.994

Gnomad SAS exome

AF:

0.961

Gnomad FIN exome

AF:

0.919

Gnomad NFE exome

AF:

0.914

Gnomad OTH exome

AF:

0.925

GnomAD4 exome

AF:

0.916

AC:

1262982

AN:

1378828

Hom.:

579581

Cov.:

AF XY:

0.918

AC XY:

624457

AN XY:

680092

show subpopulations

Gnomad4 AFR exome

AF:

0.698

Gnomad4 AMR exome

AF:

0.941

Gnomad4 ASJ exome

AF:

0.926

Gnomad4 EAS exome

AF:

0.996

Gnomad4 SAS exome

AF:

0.960

Gnomad4 FIN exome

AF:

0.924

Gnomad4 NFE exome

AF:

0.915

Gnomad4 OTH exome

AF:

0.911

GnomAD4 genome

AF:

0.865

AC:

131647

AN:

152238

Hom.:

57704

Cov.:

AF XY:

0.869

AC XY:

64655

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.709

Gnomad4 AMR

AF:

0.913

Gnomad4 ASJ

AF:

0.922

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.958

Gnomad4 FIN

AF:

0.928

Gnomad4 NFE

AF:

0.918

Gnomad4 OTH

AF:

0.880

Alfa

AF:

0.898

Hom.:

16800

Bravo

AF:

0.855

Asia WGS

AF:

0.963

AC:

3346

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over