Variant 5-176955994-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001199298.2(UIMC1):c.1304C>T(p.Pro435Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,612,168 control chromosomes in the GnomAD database, including 24,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1670 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22857 hom. )

Consequence

UIMC1
NM_001199298.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.44

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015190542).

BP6

Variant 5-176955994-G-A is Benign according to our data. Variant chr5-176955994-G-A is described in ClinVar as [Benign]. Clinvar id is 1275697.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UIMC1	NM_001199298.2 linkuse as main transcript	c.1304C>T	p.Pro435Leu	missense_variant	8/15	ENST00000511320.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UIMC1	ENST00000511320.6 linkuse as main transcript	c.1304C>T	p.Pro435Leu	missense_variant	8/15	1	NM_001199298.2	P1	Q96RL1-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19784

AN:

152026

Hom.:

1668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.0753

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.0478

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.141

AC:

35351

AN:

250244

Hom.:

3063

AF XY:

0.142

AC XY:

19218

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.0360

Gnomad AMR exome

AF:

0.0614

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.0907

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.170

AC:

248834

AN:

1460022

Hom.:

22857

Cov.:

AF XY:

0.168

AC XY:

122282

AN XY:

726378

show subpopulations

Gnomad4 AFR exome

AF:

0.0340

Gnomad4 AMR exome

AF:

0.0649

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.0924

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.130

AC:

19786

AN:

152146

Hom.:

1670

Cov.:

AF XY:

0.132

AC XY:

9809

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0411

Gnomad4 AMR

AF:

0.0752

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.158

Hom.:

4131

Bravo

AF:

0.114

TwinsUK

AF:

0.176

AC:

654

ALSPAC

AF:

0.182

AC:

701

ESP6500AA

AF:

0.0436

AC:

192

ESP6500EA

AF:

0.174

AC:

1496

ExAC

AF:

0.142

AC:

17248

Asia WGS

AF:

0.137

AC:

478

AN:

3478

EpiCase

AF:

0.160

EpiControl

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 26, 2021

This variant is associated with the following publications: (PMID: 32039725) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.;T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

.;D;D;D

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

M;.;M;.

MutationTaster

Benign

0.00059

P;P;P;P

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.3

D;D;D;.

REVEL

Benign

0.084

Sift

Uncertain

0.0090

D;D;D;.

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.96

D;.;D;D

Vest4

0.30

MPC

0.48

ClinPred

0.025

GERP RS

5.5

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.12

gMVP

0.13

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