5-176951573-G-T

Variant names:

• chr5-176951573-G-T
• rs365132
• NM_001199298.2:c.1344C>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.263
• Publications: 77 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.1344C>A	p.Thr448Thr	synonymous_variant	Exon 9 of 15	ENST00000511320.6	NP_001186227.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87678 AN: 151834 Hom.: 27018 Cov.: 32

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

GnomAD2 exomes AF: 0.510 AC: 109445 AN: 214716 AF XY: 0.506

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 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.: 30 AF XY: 0.496 AC XY: 346886 AN XY: 699330

African (AFR) AF: 0.826 AC: 25485 AN: 30844

American (AMR) AF: 0.380 AC: 12826 AN: 33756

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 13246 AN: 24664

East Asian (EAS) AF: 0.498 AC: 18852 AN: 37892

South Asian (SAS) AF: 0.477 AC: 35791 AN: 75034

European-Finnish (FIN) AF: 0.502 AC: 26480 AN: 52744

Middle Eastern (MID) AF: 0.595 AC: 3340 AN: 5610

European-Non Finnish (NFE) AF: 0.489 AC: 533226 AN: 1089388

Other (OTH) AF: 0.513 AC: 29802 AN: 58150

GnomAD4 genome AF: 0.578 AC: 87787 AN: 151952 Hom.: 27071 Cov.: 32 AF XY: 0.574 AC XY: 42618 AN XY: 74248

African (AFR) AF: 0.811 AC: 33644 AN: 41486

American (AMR) AF: 0.425 AC: 6476 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1846 AN: 3472

East Asian (EAS) AF: 0.491 AC: 2539 AN: 5172

South Asian (SAS) AF: 0.503 AC: 2420 AN: 4812

European-Finnish (FIN) AF: 0.500 AC: 5255 AN: 10512

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33760 AN: 67938

Other (OTH) AF: 0.545 AC: 1152 AN: 2114

Alfa AF: 0.527 Hom.: 75445

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

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
PhyloP100		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs365132; hg19: chr5-176378574; COSMIC: COSV65894610;