Genetic Variant UIMC1:p.Asn525Ile (chr5-176943358-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001199298.2(UIMC1):c.1574A>T(p.Asn525Ile) 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 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N525S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UIMC1
NM_001199298.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.323

Publications

0 publications found

Variant links:

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)

UIMC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UIMC1	NM_001199298.2	MANE Select	c.1574A>T	p.Asn525Ile	missense	Exon 10 of 15	NP_001186227.1	Q96RL1-1
UIMC1	NM_001199297.2		c.1574A>T	p.Asn525Ile	missense	Exon 11 of 16	NP_001186226.1	Q96RL1-1
UIMC1	NM_016290.4		c.1574A>T	p.Asn525Ile	missense	Exon 10 of 15	NP_057374.3	Q96RL1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UIMC1	ENST00000511320.6	TSL:1 MANE Select	c.1574A>T	p.Asn525Ile	missense	Exon 10 of 15	ENSP00000421926.1	Q96RL1-1
UIMC1	ENST00000377227.8	TSL:1	c.1574A>T	p.Asn525Ile	missense	Exon 10 of 15	ENSP00000366434.4	Q96RL1-1
UIMC1	ENST00000506128.5	TSL:1	c.1076A>T	p.Asn359Ile	missense	Exon 10 of 15	ENSP00000427480.1	Q96RL1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111978

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.41

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.6

PhyloP100

0.32

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-6.4

REVEL

Benign

0.11

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0010

Polyphen

0.34

Vest4

0.67

MutPred

0.39

Loss of disorder (P = 0.0545)

MVP

0.16

MPC

0.60

ClinPred

0.91

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.44

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over