rs140185789

Variant names:

• chr5-176905430-C-G
• rs140185789
• NM_001199298.2:c.2012G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-176905430-C-G
• chr5-176905430-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001199298.2(UIMC1):​c.2012G>C​(p.Arg671Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. R671H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: UIMC1 NM_001199298.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 5 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0322088).

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.2012G>C	p.Arg671Pro	missense	Exon 15 of 15	NP_001186227.1	Q96RL1-1
	UIMC1	NM_001199297.2		c.2012G>C	p.Arg671Pro	missense	Exon 16 of 16	NP_001186226.1	Q96RL1-1
	UIMC1	NM_016290.4		c.2012G>C	p.Arg671Pro	missense	Exon 15 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.2012G>C	p.Arg671Pro	missense	Exon 15 of 15	ENSP00000421926.1	Q96RL1-1
	UIMC1	ENST00000377227.8	TSL:1	c.2012G>C	p.Arg671Pro	missense	Exon 15 of 15	ENSP00000366434.4	Q96RL1-1
	UIMC1	ENST00000506128.5	TSL:1	c.1514G>C	p.Arg505Pro	missense	Exon 15 of 15	ENSP00000427480.1	Q96RL1-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251282 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33470

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

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

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39698

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111980

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5208

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000494 AC: 6

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.4
DANN	Benign	0.67
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.13
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.029
Sift	Uncertain	0.028	D
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.074
MutPred		0.12		Gain of loop (P = 0.024)
MVP		0.15
MPC		0.30
ClinPred		0.020	T
GERP RS		1.1
Varity_R		0.19
gMVP		0.088
Mutation Taster		=96/4	polymorphism

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: rs140185789; hg19: chr5-176332431;