NM_001199298.2:c.1756G>A

Variant names:

• chr5-176908615-C-T
• rs144604125
• NM_001199298.2:c.1756G>A

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.1756G>A​(p.Ala586Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A586S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UIMC1 NM_001199298.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23
• Publications: 4 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)

ENSG00000298307 (HGNC:):

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=0.14728597).

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.1756G>A	p.Ala586Thr	missense	Exon 12 of 15	NP_001186227.1	Q96RL1-1
	UIMC1	NM_001199297.2		c.1756G>A	p.Ala586Thr	missense	Exon 13 of 16	NP_001186226.1	Q96RL1-1
	UIMC1	NM_016290.4		c.1756G>A	p.Ala586Thr	missense	Exon 12 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.1756G>A	p.Ala586Thr	missense	Exon 12 of 15	ENSP00000421926.1	Q96RL1-1
	UIMC1	ENST00000377227.8	TSL:1	c.1756G>A	p.Ala586Thr	missense	Exon 12 of 15	ENSP00000366434.4	Q96RL1-1
	UIMC1	ENST00000506128.5	TSL:1	c.1258G>A	p.Ala420Thr	missense	Exon 12 of 15	ENSP00000427480.1	Q96RL1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251172 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.2
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.091
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Polyphen		0.87	P
Vest4		0.30
MutPred		0.22		Loss of stability (P = 0.0209)
MVP		0.42
MPC		0.63
ClinPred		0.77	D
GERP RS		5.0
Varity_R		0.23
gMVP		0.10
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs144604125; hg19: chr5-176335616;