chr1-241519696-C-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP7
The NM_000143.4(FH):c.27G>T(p.Ala9Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A9A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
FH
NM_000143.4 synonymous
NM_000143.4 synonymous
Scores
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.240
Publications
0 publications found
Genes affected
FH (HGNC:3700): (fumarate hydratase) The protein encoded by this gene is an enzymatic component of the tricarboxylic acid (TCA) cycle, or Krebs cycle, and catalyzes the formation of L-malate from fumarate. It exists in both a cytosolic form and an N-terminal extended form, differing only in the translation start site used. The N-terminal extended form is targeted to the mitochondrion, where the removal of the extension generates the same form as in the cytoplasm. It is similar to some thermostable class II fumarases and functions as a homotetramer. Mutations in this gene can cause fumarase deficiency and lead to progressive encephalopathy. [provided by RefSeq, Jul 2008]
FH Gene-Disease associations (from GenCC):
- hereditary leiomyomatosis and renal cell cancerInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
- fumaric aciduriaInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
- pheochromocytoma-paragangliomaInheritance: AD Classification: STRONG Submitted by: Ambry Genetics
- leiomyosarcomaInheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- hereditary pheochromocytoma-paragangliomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP7
Synonymous conserved (PhyloP=0.24 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| FH | NM_000143.4 | c.27G>T | p.Ala9Ala | synonymous_variant | Exon 1 of 10 | ENST00000366560.4 | NP_000134.2 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1394386Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 687454
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1394386
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
687454
African (AFR)
AF:
AC:
0
AN:
31338
American (AMR)
AF:
AC:
0
AN:
35558
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25092
East Asian (EAS)
AF:
AC:
0
AN:
35642
South Asian (SAS)
AF:
AC:
0
AN:
78874
European-Finnish (FIN)
AF:
AC:
0
AN:
48260
Middle Eastern (MID)
AF:
AC:
0
AN:
4142
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1077770
Other (OTH)
AF:
AC:
0
AN:
57710
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Uncertain
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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