Variant 5-176968617-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000511320.6(UIMC1):c.1138T>C(p.Ser380Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,613,604 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 7 hom. )

Consequence

UIMC1
ENST00000511320.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92

Variant links:

Genes affected

UIMC1 (HGNC:30298): (ubiquitin interaction motif containing 1) This gene encodes a nuclear protein that interacts with Brca1 (breast cancer 1) in a complex to recognize and repair DNA lesions. This protein binds ubiquitinated lysine 63 of histone H2A and H2AX. This protein may also function as a repressor of transcription. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

UIMC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031056702).

BP6

Variant 5-176968617-A-G is Benign according to our data. Variant chr5-176968617-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 437212.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UIMC1	NM_001199298.2 linkuse as main transcript	c.1138T>C	p.Ser380Pro	missense_variant	6/15	ENST00000511320.6	NP_001186227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UIMC1	ENST00000511320.6 linkuse as main transcript	c.1138T>C	p.Ser380Pro	missense_variant	6/15	1	NM_001199298.2	ENSP00000421926	P1	Q96RL1-1

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00134

AC:

336

AN:

250972

Hom.:

AF XY:

0.00139

AC XY:

188

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000610

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000852

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00198

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00168

AC:

2452

AN:

1461426

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1236

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000605

Gnomad4 ASJ exome

AF:

0.00425

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000824

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.00189

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00124

AC:

188

AN:

152178

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00119

AC:

145

EpiCase

AF:

0.00158

EpiControl

AF:

0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 19, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.17

DEOGEN2

Benign

0.040

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.44

.;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.7

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

2.6

N;N

REVEL

Benign

0.061

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.036

MVP

0.12

MPC

0.19

ClinPred

0.0012

GERP RS

0.63

Varity_R

0.045

gMVP

0.053

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