Genetic Variant UBL7:p.Arg114Pro (chr15-74452342-C-G) – 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_032907.5(UBL7):c.341G>C(p.Arg114Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,409,424 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

UBL7
NM_032907.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

Publications

0 publications found

Variant links:

Genes affected

UBL7 (HGNC:28221): (ubiquitin like 7) Predicted to enable polyubiquitin modification-dependent protein binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

UBL7 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_032907.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBL7	NM_032907.5	MANE Select	c.341G>C	p.Arg114Pro	missense	Exon 4 of 11	NP_116296.1	Q96S82
UBL7	NM_001286741.2		c.461G>C	p.Arg154Pro	missense	Exon 4 of 11	NP_001273670.1
UBL7	NM_001286742.2		c.461G>C	p.Arg154Pro	missense	Exon 5 of 12	NP_001273671.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBL7	ENST00000395081.7	TSL:1 MANE Select	c.341G>C	p.Arg114Pro	missense	Exon 4 of 11	ENSP00000378518.2	Q96S82
UBL7	ENST00000564488.5	TSL:1	c.341G>C	p.Arg114Pro	missense	Exon 5 of 12	ENSP00000454828.1	Q96S82
UBL7	ENST00000565335.5	TSL:1	c.341G>C	p.Arg114Pro	missense	Exon 5 of 12	ENSP00000457708.1	Q96S82

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000581

AC:

AN:

171976

AF XY:

0.0000110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1409424

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

696036

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

32430

American (AMR)

AF:

0.0000270

AC:

AN:

37090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25258

East Asian (EAS)

AF:

0.00

AC:

AN:

37124

South Asian (SAS)

AF:

0.00

AC:

AN:

80098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083754

Other (OTH)

AF:

0.00

AC:

AN:

58344

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.088

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.0

PhyloP100

6.1

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.30

Sift

Benign

0.14

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.76

MutPred

0.58

Loss of MoRF binding (P = 0.0129)

MVP

0.66

MPC

1.1

ClinPred

0.82

GERP RS

5.5

PromoterAI

-0.058

Neutral

(source)

Varity_R

0.61

gMVP

0.87

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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