rs150697112

chr5-176968617-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001199298.2(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 NM_001199298.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92

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]

ACMG classification

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 GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UIMC1	NM_001199298.2	c.1138T>C	p.Ser380Pro	missense_variant	6/15	ENST00000511320.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UIMC1	ENST00000511320.6	c.1138T>C	p.Ser380Pro	missense_variant	6/15	1	NM_001199298.2	P1

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 188 AN: 152060 Hom.: 0 Cov.: 32

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.: 2 AF XY: 0.00139 AC XY: 188 AN XY: 135654

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.: 7 Cov.: 31 AF XY: 0.00170 AC XY: 1236 AN XY: 727030

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.: 0 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74398

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.: 1

Bravo AF: 0.00110

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00174 AC: 15

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

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	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	11
Dann	Benign	0.17
DEOGEN2	Benign	0.040	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.032	N
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.0031	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.7	N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.27	T
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	T
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

Other links and lift over

dbSNP: rs150697112; hg19: chr5-176395618;