Variant NM_001199298.2:c.1344C>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001199298.2(UIMC1):c.1344C>A(p.Thr448Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,560,034 control chromosomes in the GnomAD database, including 203,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.58 ( 27071 hom., cov: 32)

Exomes 𝑓: 0.50 ( 176217 hom. )

Consequence

UIMC1
NM_001199298.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.263

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 5-176951573-G-T is Benign according to our data. Variant chr5-176951573-G-T is described in ClinVar as [Benign]. Clinvar id is 1770419.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.263 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UIMC1	NM_001199298.2 link	c.1344C>A	p.Thr448Thr	synonymous_variant	Exon 9 of 15	ENST00000511320.6	NP_001186227.1	Q96RL1-1A0A024R7R0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UIMC1	ENST00000511320.6 link	c.1344C>A	p.Thr448Thr	synonymous_variant	Exon 9 of 15	1	NM_001199298.2	ENSP00000421926.1		Q96RL1-1
UIMC1	ENST00000506128.5 link	c.846C>A	p.Thr282Thr	synonymous_variant	Exon 9 of 15	1		ENSP00000427480.1		Q96RL1-2

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87678

AN:

151834

Hom.:

27018

Cov.:

show subpopulations

Gnomad AFR

AF:

0.811

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.543

GnomAD3 exomes

AF:

0.510

AC:

109445

AN:

214716

Hom.:

28745

AF XY:

0.506

AC XY:

59141

AN XY:

116884

show subpopulations

Gnomad AFR exome

AF:

0.819

Gnomad AMR exome

AF:

0.369

Gnomad ASJ exome

AF:

0.543

Gnomad EAS exome

AF:

0.494

Gnomad SAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.505

Gnomad NFE exome

AF:

0.507

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.496

AC:

699048

AN:

1408082

Hom.:

176217

Cov.:

AF XY:

0.496

AC XY:

346886

AN XY:

699330

show subpopulations

Gnomad4 AFR exome

AF:

0.826

Gnomad4 AMR exome

AF:

0.380

Gnomad4 ASJ exome

AF:

0.537

Gnomad4 EAS exome

AF:

0.498

Gnomad4 SAS exome

AF:

0.477

Gnomad4 FIN exome

AF:

0.502

Gnomad4 NFE exome

AF:

0.489

Gnomad4 OTH exome

AF:

0.513

GnomAD4 genome

AF:

0.578

AC:

87787

AN:

151952

Hom.:

27071

Cov.:

AF XY:

0.574

AC XY:

42618

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.811

Gnomad4 AMR

AF:

0.425

Gnomad4 ASJ

AF:

0.532

Gnomad4 EAS

AF:

0.491

Gnomad4 SAS

AF:

0.503

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.497

Gnomad4 OTH

AF:

0.545

Alfa

AF:

0.516

Hom.:

34531

Bravo

AF:

0.580

Asia WGS

AF:

0.544

AC:

1893

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 15, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.9

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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