7-27662716-C-A

Variant summary

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

The NM_152740.4(HIBADH):​c.73G>T​(p.Ala25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 1,374,700 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

HIBADH
NM_152740.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0170
Variant links:
Genes affected
HIBADH (HGNC:4907): (3-hydroxyisobutyrate dehydrogenase) This gene encodes a mitochondrial 3-hydroxyisobutyrate dehydrogenase enzyme. The encoded protein plays a critical role in the catabolism of L-valine by catalyzing the oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde. [provided by RefSeq, Nov 2011]

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=0.08366531).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HIBADHNM_152740.4 linkuse as main transcriptc.73G>T p.Ala25Ser missense_variant 1/8 ENST00000265395.7
LOC105375211XR_007060268.1 linkuse as main transcriptn.136+10066C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HIBADHENST00000265395.7 linkuse as main transcriptc.73G>T p.Ala25Ser missense_variant 1/81 NM_152740.4 P1
HIBADHENST00000496814.1 linkuse as main transcriptn.142G>T non_coding_transcript_exon_variant 1/23
HIBADHENST00000428288.2 linkuse as main transcriptc.73G>T p.Ala25Ser missense_variant, NMD_transcript_variant 1/73

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152216
Hom.:
0
Cov.:
32
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
36
AN:
1222484
Hom.:
0
Cov.:
30
AF XY:
0.0000320
AC XY:
19
AN XY:
593430
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:
0.0000313
Gnomad4 OTH exome
AF:
0.000102
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2023HIBADH: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
13
DANN
Benign
0.95
DEOGEN2
Benign
0.14
T
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.084
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
0.040
N
REVEL
Benign
0.044
Sift
Benign
0.60
T
Sift4G
Benign
0.80
T
Polyphen
0.023
B
Vest4
0.11
MutPred
0.45
Gain of glycosylation at A25 (P = 0.0019);
MVP
0.21
MPC
0.044
ClinPred
0.12
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.050
gMVP
0.43

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: rs901133047; hg19: chr7-27702335; API