19-15125032-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006844.5(ILVBL):​c.28G>A​(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,563,704 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: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

ILVBL
NM_006844.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.192
Variant links:
Genes affected
ILVBL (HGNC:6041): (ilvB acetolactate synthase like) The protein encoded by this gene shares similarity with several thiamine pyrophosphate-binding proteins identified in bacteria, yeast, and plants. The highest degree of similarity is found with bacterial acetolactate synthases (AHAS), which are enzymes that catalyze the first step in branched-chain amino acid biosynthesis. [provided by RefSeq, Jul 2008]
ILVBL-AS1 (HGNC:55279): (ILVBL antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08937645).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ILVBLNM_006844.5 linkc.28G>A p.Ala10Thr missense_variant Exon 2 of 16 ENST00000263383.8 NP_006835.2 A1L0T0
ILVBLXM_005259717.5 linkc.28G>A p.Ala10Thr missense_variant Exon 2 of 16 XP_005259774.1 A1L0T0
ILVBLXM_011527651.3 linkc.-187+38G>A intron_variant Intron 1 of 14 XP_011525953.1 M0R026
ILVBL-AS1NR_186314.1 linkn.108+527C>T intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ILVBLENST00000263383.8 linkc.28G>A p.Ala10Thr missense_variant Exon 2 of 16 1 NM_006844.5 ENSP00000263383.3 A1L0T0

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000608
AC:
1
AN:
164364
Hom.:
0
AF XY:
0.0000113
AC XY:
1
AN XY:
88618
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000152
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000354
AC:
50
AN:
1411482
Hom.:
0
Cov.:
30
AF XY:
0.0000373
AC XY:
26
AN XY:
697472
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000460
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152222
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.28G>A (p.A10T) alteration is located in exon 2 (coding exon 1) of the ILVBL gene. This alteration results from a G to A substitution at nucleotide position 28, causing the alanine (A) at amino acid position 10 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
0.094
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
11
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T;T;T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.65
T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.089
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
M;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.080
N;N;N
REVEL
Benign
0.020
Sift
Benign
0.043
D;D;D
Sift4G
Benign
0.25
T;.;T
Polyphen
0.70
P;.;.
Vest4
0.25
MutPred
0.27
Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);
MVP
0.19
MPC
0.44
ClinPred
0.14
T
GERP RS
2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.065
gMVP
0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs568556685; hg19: chr19-15235843; API