rs1466918215

Variant summary

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

The NM_005327.7(HADH):​c.28C>A​(p.Arg10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,602 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HADH
NM_005327.7 missense

Scores

13
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38
Variant links:
Genes affected
HADH (HGNC:4799): (hydroxyacyl-CoA dehydrogenase) This gene is a member of the 3-hydroxyacyl-CoA dehydrogenase gene family. The encoded protein functions in the mitochondrial matrix to catalyze the oxidation of straight-chain 3-hydroxyacyl-CoAs as part of the beta-oxidation pathway. Its enzymatic activity is highest with medium-chain-length fatty acids. Mutations in this gene cause one form of familial hyperinsulinemic hypoglycemia. The human genome contains a related pseudogene of this gene on chromosome 15. [provided by RefSeq, May 2010]
CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)

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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 rank MANE Protein UniProt
HADHNM_005327.7 linkc.28C>A p.Arg10Ser missense_variant Exon 1 of 8 ENST00000309522.8 NP_005318.6 Q16836-1A0A140VK76
HADHNM_001184705.4 linkc.28C>A p.Arg10Ser missense_variant Exon 1 of 9 NP_001171634.3 Q16836-3
HADHXR_007096395.1 linkn.72C>A non_coding_transcript_exon_variant Exon 1 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HADHENST00000309522.8 linkc.28C>A p.Arg10Ser missense_variant Exon 1 of 8 1 NM_005327.7 ENSP00000312288.4 Q16836-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460602
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726614
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
.;.;T;.;.
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.90
D;D;D;D;D
M_CAP
Uncertain
0.27
D
MetaRNN
Uncertain
0.67
D;D;D;D;D
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Benign
1.9
.;L;L;.;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.6
.;.;N;.;N
REVEL
Uncertain
0.38
Sift
Benign
0.11
.;.;T;.;T
Sift4G
Benign
0.35
.;T;T;.;.
Polyphen
0.83
.;.;P;.;.
Vest4
0.69, 0.68
MutPred
0.42
.;Gain of glycosylation at S11 (P = 0.0101);Gain of glycosylation at S11 (P = 0.0101);Gain of glycosylation at S11 (P = 0.0101);Gain of glycosylation at S11 (P = 0.0101);
MVP
0.89
MPC
0.52
ClinPred
0.96
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.50
gMVP
0.61

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: chr4-108911116; API