Genetic Variant UBALD1:p.Ala152Thr (chr16-4609713-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145253.3(UBALD1):c.454G>A(p.Ala152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBALD1
NM_145253.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.510

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02626744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBALD1	NM_145253.3 link	c.454G>A	p.Ala152Thr	missense_variant	Exon 3 of 3	ENST00000283474.12	NP_660296.1	Q8TB05-1
UBALD1	NM_001330467.2 link	c.379G>A	p.Ala127Thr	missense_variant	Exon 3 of 3		NP_001317396.1	Q8TB05K7EM88
UBALD1	NM_001411032.1 link	c.*270G>A		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.454G>A	p.Ala152Thr	missense_variant	Exon 3 of 3	1	NM_145253.3	ENSP00000283474.6		Q8TB05-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1323128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

646532

African (AFR)

AF:

0.00

AC:

AN:

27672

American (AMR)

AF:

0.00

AC:

AN:

24602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18592

East Asian (EAS)

AF:

0.00

AC:

AN:

35176

South Asian (SAS)

AF:

0.00

AC:

AN:

65024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4540

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1046528

Other (OTH)

AF:

0.00

AC:

AN:

54112

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 13, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.454G>A (p.A152T) alteration is located in exon 3 (coding exon 3) of the UBALD1 gene. This alteration results from a G to A substitution at nucleotide position 454, causing the alanine (A) at amino acid position 152 to be replaced by a threonine (T). 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

0.067

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0016

.;.;T;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.64

T;T;T;T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.026

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;.;N;.;.

PhyloP100

0.51

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.46

.;.;N;.;.

REVEL

Benign

0.065

Sift

Benign

1.0

.;.;T;.;.

Sift4G

Benign

0.44

T;T;T;T;T

Polyphen

0.0

.;.;B;B;.

Vest4

0.061

MutPred

0.18

.;.;Gain of glycosylation at A152 (P = 0.0019);.;.;

MVP

0.11

MPC

0.16

ClinPred

0.20

GERP RS

-0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.15

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over