2-190205160-T-C

Position:

• chr2-190205160-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014362.4(HIBCH):​c.1118A>G​(p.Asn373Ser) 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. 15/21 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)
• Consequence: HIBCH NM_014362.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.39

Genes affected

HIBCH (HGNC:4908): (3-hydroxyisobutyryl-CoA hydrolase) This gene encodes the enzyme responsible for hydrolysis of both HIBYL-CoA and beta-hydroxypropionyl-CoA. Mutations in this gene have been associated with 3-hyroxyisobutyryl-CoA hydrolase deficiency. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

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=0.088157624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBCH	NM_014362.4	c.1118A>G	p.Asn373Ser	missense_variant	14/14	ENST00000359678.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBCH	ENST00000359678.10	c.1118A>G	p.Asn373Ser	missense_variant	14/14	1	NM_014362.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Pediatric Department, Xiangya Hospital, Central South University

-

This variant was observed in compound heterozygosity with variant (c.810-4A>G) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.28	N;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.071
Sift	Benign	0.10	T;T
Sift4G	Benign	0.16	T;D
Polyphen		0.0010	B;.
Vest4		0.022
MutPred		0.26		Gain of phosphorylation at N373 (P = 0.0516);.;
MVP		0.49
MPC		0.030
ClinPred		0.25	T
GERP RS		4.2
Varity_R		0.23
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-191069886; COSMIC: COSV61410902; COSMIC: COSV61410902;