Genetic Variant UBALD1:p.Pro112Arg (chr16-4609832-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145253.3(UBALD1):c.335C>G(p.Pro112Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

UBALD1
NM_145253.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97

Publications

0 publications found

Variant links:

Genes affected

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

UBALD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.19543615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3 link	c.335C>G	p.Pro112Arg	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1	Q8TB05-1
UBALD1	NM_001330467.2 link	c.260C>G	p.Pro87Arg	missense_variant	Exon 3 of 3		NP_001317396.1	Q8TB05K7EM88
UBALD1	NM_001411032.1 link	c.*151C>G		3_prime_UTR_variant	Exon 3 of 3		NP_001397961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBALD1	ENST00000283474.12 link	c.335C>G	p.Pro112Arg	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6		Q8TB05-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000619

AC:

AN:

161614

AF XY:

0.00

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1380632

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

678818

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31042

American (AMR)

AF:

0.00

AC:

AN:

33100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21120

East Asian (EAS)

AF:

0.00

AC:

AN:

38322

South Asian (SAS)

AF:

0.0000133

AC:

AN:

74960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5374

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072224

Other (OTH)

AF:

0.00

AC:

AN:

56726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000848

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.335C>G (p.P112R) alteration is located in exon 3 (coding exon 3) of the UBALD1 gene. This alteration results from a C to G substitution at nucleotide position 335, causing the proline (P) at amino acid position 112 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0056

.;.;T;T;.;.

Eigen

Benign

0.048

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

T;T;T;T;T;T

M_CAP

Benign

0.073

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;.;L;.;.;.

PhyloP100

3.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.9

.;.;N;.;.;.

REVEL

Benign

0.082

Sift

Uncertain

0.027

.;.;D;.;.;.

Sift4G

Uncertain

0.0020

D;D;D;D;D;D

Polyphen

0.90, 0.96

.;.;P;D;.;.

Vest4

0.39

MutPred

0.24

.;.;Loss of glycosylation at P112 (P = 0.0225);.;.;.;

MVP

0.15

MPC

0.17

ClinPred

0.32

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.35

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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16-4609832-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over