7-27543085-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152740.4(HIBADH):​c.500G>T​(p.Arg167Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

HIBADH
NM_152740.4 missense

Scores

2
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.99
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HIBADHNM_152740.4 linkuse as main transcriptc.500G>T p.Arg167Leu missense_variant 5/8 ENST00000265395.7
HIBADHXM_047419834.1 linkuse as main transcriptc.197G>T p.Arg66Leu missense_variant 4/7
HIBADHXM_047419835.1 linkuse as main transcriptc.197G>T p.Arg66Leu missense_variant 4/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HIBADHENST00000265395.7 linkuse as main transcriptc.500G>T p.Arg167Leu missense_variant 5/81 NM_152740.4 P1
HIBADHENST00000425715.1 linkuse as main transcriptc.329G>T p.Arg110Leu missense_variant 4/62
HIBADHENST00000428288.2 linkuse as main transcriptc.*219G>T 3_prime_UTR_variant, NMD_transcript_variant 4/73

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152136
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000290
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250736
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135488
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS 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:
0.0000178
AC:
26
AN:
1461446
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
727000
show subpopulations
Gnomad4 AFR exome
AF:
0.000718
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152136
Hom.:
0
Cov.:
31
AF XY:
0.000135
AC XY:
10
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.000290
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000953
Hom.:
0
Bravo
AF:
0.000144
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T
Eigen
Benign
0.084
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.52
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.13
Sift
Benign
0.048
D
Sift4G
Benign
0.18
T
Polyphen
0.040
B
Vest4
0.73
MVP
0.41
MPC
0.055
ClinPred
0.42
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.67
gMVP
0.81

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: rs768479109; hg19: chr7-27582704; API