chr5-176943463-T-C

Position:

• chr5-176943463-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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 Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UIMC1	NM_001199298.2	c.1469A>G	p.Lys490Arg	missense_variant	10/15	ENST00000511320.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UIMC1	ENST00000511320.6	c.1469A>G	p.Lys490Arg	missense_variant	10/15	1	NM_001199298.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.1469A>G (p.K490R) alteration is located in exon 10 (coding exon 9) of the UIMC1 gene. This alteration results from a A to G substitution at nucleotide position 1469, causing the lysine (K) at amino acid position 490 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.65	.;T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;M;.
MutationTaster	Benign	0.91	N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N;N;N;.
REVEL	Benign	0.052
Sift	Benign	0.099	T;T;T;.
Sift4G	Benign	0.34	T;T;T;T
Polyphen		1.0	D;.;D;D
Vest4		0.20
MutPred		0.20		Loss of ubiquitination at K490 (P = 0.002);.;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-176370464;