chr5-176908564-T-G

Variant names:

• chr5-176908564-T-G
• NM_001199298.2:c.1807A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199298.2(UIMC1):​c.1807A>C​(p.Thr603Pro) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UIMC1 NM_001199298.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.93

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05402893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UIMC1	NM_001199298.2	c.1807A>C	p.Thr603Pro	missense_variant	Exon 12 of 15	ENST00000511320.6	NP_001186227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UIMC1	ENST00000511320.6	c.1807A>C	p.Thr603Pro	missense_variant	Exon 12 of 15	1	NM_001199298.2	ENSP00000421926.1
UIMC1	ENST00000506128.5	c.1309A>C	p.Thr437Pro	missense_variant	Exon 12 of 15	1		ENSP00000427480.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1807A>C (p.T603P) alteration is located in exon 12 (coding exon 11) of the UIMC1 gene. This alteration results from a A to C substitution at nucleotide position 1807, causing the threonine (T) at amino acid position 603 to be replaced by a proline (P). 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	0.065
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.010
DANN	Benign	0.56
DEOGEN2	Benign	0.015	T;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.38	.;T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.054	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.12	N;.;N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.55	N;N;N;.
REVEL	Benign	0.023
Sift	Benign	0.29	T;T;T;.
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.0010	B;.;B;B
Vest4		0.086
MutPred		0.21		Loss of sheet (P = 0.0126);.;Loss of sheet (P = 0.0126);.;
MVP		0.10
MPC		0.19
ClinPred		0.062	T
GERP RS		-6.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.044
gMVP		0.067

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-176335565;