Variant 7-27662700-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152740.4(HIBADH):c.89C>T(p.Ala30Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,200,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

HIBADH
NM_152740.4 missense, splice_region

Scores

Splicing: ADA: 0.002839

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.176

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]

HIBADH links:

LOC105375211 (HGNC:):

LOC105375211 links:

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=0.08221465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBADH	NM_152740.4 linkuse as main transcript	c.89C>T	p.Ala30Val	missense_variant, splice_region_variant	1/8	ENST00000265395.7
LOC105375211	XR_007060268.1 linkuse as main transcript	n.136+10050G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HIBADH	ENST00000265395.7 linkuse as main transcript	c.89C>T	p.Ala30Val	missense_variant, splice_region_variant	1/8	1	NM_152740.4	P1
HIBADH	ENST00000496814.1 linkuse as main transcript	n.158C>T		splice_region_variant, non_coding_transcript_exon_variant	1/2	3
HIBADH	ENST00000428288.2 linkuse as main transcript	c.89C>T	p.Ala30Val	missense_variant, splice_region_variant, NMD_transcript_variant	1/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1200402

Hom.:

Cov.:

AF XY:

0.00000344

AC XY:

AN XY:

580692

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:

0.0000196

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000512

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.89C>T (p.A30V) alteration is located in exon 1 (coding exon 1) of the HIBADH gene. This alteration results from a C to T substitution at nucleotide position 89, causing the alanine (A) at amino acid position 30 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.14

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.44

M_CAP

Benign

0.0089

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.22

REVEL

Benign

0.029

Sift

Benign

0.51

Sift4G

Benign

0.61

Polyphen

0.0010

Vest4

0.079

MutPred

0.38

Loss of disorder (P = 0.0893);

MVP

0.16

MPC

0.046

ClinPred

0.21

GERP RS

-0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.033

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0028

dbscSNV1_RF

Benign

0.18

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over