5-176943463-T-C

Variant names:

• chr5-176943463-T-C
• NM_001199298.2:c.1469A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199298.2(UIMC1):​c.1469A>G​(p.Lys490Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UIMC1 NM_001199298.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15533409).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199298.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UIMC1	NM_001199298.2	MANE Select	c.1469A>G	p.Lys490Arg	missense	Exon 10 of 15	NP_001186227.1	Q96RL1-1
	UIMC1	NM_001199297.2		c.1469A>G	p.Lys490Arg	missense	Exon 11 of 16	NP_001186226.1	Q96RL1-1
	UIMC1	NM_016290.4		c.1469A>G	p.Lys490Arg	missense	Exon 10 of 15	NP_057374.3	Q96RL1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UIMC1	ENST00000511320.6	TSL:1 MANE Select	c.1469A>G	p.Lys490Arg	missense	Exon 10 of 15	ENSP00000421926.1	Q96RL1-1
	UIMC1	ENST00000377227.8	TSL:1	c.1469A>G	p.Lys490Arg	missense	Exon 10 of 15	ENSP00000366434.4	Q96RL1-1
	UIMC1	ENST00000506128.5	TSL:1	c.971A>G	p.Lys324Arg	missense	Exon 10 of 15	ENSP00000427480.1	Q96RL1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.7
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.052
Sift	Benign	0.099	T
Sift4G	Benign	0.34	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.20		Loss of ubiquitination at K490 (P = 0.002)
MVP		0.36
MPC		0.15
ClinPred		0.45	T
GERP RS		4.8
Varity_R		0.049
gMVP		0.074
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

hg19: chr5-176370464;