Genetic Variant UBALD1:p.Met62Ile (chr16-4609981-C-T) – 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_145253.3(UBALD1):c.186G>A(p.Met62Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000635 in 1,573,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

UBALD1
NM_145253.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Publications

0 publications found

Variant links:

Genes affected

UBALD1 (HGNC:29576): (UBA like domain containing 1)

UBALD1 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_145253.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBALD1	NM_145253.3	MANE Select	c.186G>A	p.Met62Ile	missense splice_region	Exon 3 of 3	NP_660296.1	Q8TB05-1
UBALD1	NM_001411032.1		c.*2G>A		splice_region	Exon 3 of 3	NP_001397961.1	K7EKR5
UBALD1	NM_001411032.1		c.*2G>A		3_prime_UTR	Exon 3 of 3	NP_001397961.1	K7EKR5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBALD1	ENST00000283474.12	TSL:1 MANE Select	c.186G>A	p.Met62Ile	missense splice_region	Exon 3 of 3	ENSP00000283474.6	Q8TB05-1
UBALD1	ENST00000590891.1	TSL:6	c.291G>A	p.Met97Ile	missense	Exon 1 of 1	ENSP00000465706.1	Q8TB05-2
UBALD1	ENST00000591401.5	TSL:5	c.123G>A	p.Met41Ile	missense splice_region	Exon 2 of 2	ENSP00000467671.1	K7EQ49

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151438

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000492

AC:

AN:

1422468

Hom.:

Cov.:

AF XY:

0.00000426

AC XY:

AN XY:

704360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32952

American (AMR)

AF:

0.00

AC:

AN:

40872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24216

East Asian (EAS)

AF:

0.00

AC:

AN:

38990

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81336

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.00000550

AC:

AN:

1090308

Other (OTH)

AF:

0.00

AC:

AN:

58840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151438

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41148

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000443

AC:

AN:

67790

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

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

0.82

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.45

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.4

PhyloP100

6.0

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.25

Sift

Benign

0.041

Sift4G

Uncertain

0.030

Polyphen

0.29

Vest4

0.54

MutPred

0.31

Gain of sheet (P = 0.0344)

MVP

0.47

MPC

0.24

ClinPred

0.96

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.61

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over