1-241500602-TGAGAGAGAGAGAGAGAGA-TGAGAGAGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000143.4(FH):​c.1237-22_1237-13delTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000912 in 1,490,698 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000075 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

FH
NM_000143.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.18
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 1-241500602-TGAGAGAGAGA-T is Benign according to our data. Variant chr1-241500602-TGAGAGAGAGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 2575507.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000929 (126/1356806) while in subpopulation AFR AF= 0.000767 (24/31294). AF 95% confidence interval is 0.000528. There are 0 homozygotes in gnomad4_exome. There are 51 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FHNM_000143.4 linkc.1237-22_1237-13delTCTCTCTCTC intron_variant Intron 8 of 9 ENST00000366560.4 NP_000134.2 P07954-1A0A0S2Z4C3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FHENST00000366560.4 linkc.1237-22_1237-13delTCTCTCTCTC intron_variant Intron 8 of 9 1 NM_000143.4 ENSP00000355518.4 P07954-1

Frequencies

GnomAD3 genomes
AF:
0.0000747
AC:
10
AN:
133802
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000287
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000760
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000217
Gnomad SAS
AF:
0.000246
Gnomad FIN
AF:
0.000141
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000784
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000929
AC:
126
AN:
1356806
Hom.:
0
AF XY:
0.0000755
AC XY:
51
AN XY:
675462
show subpopulations
Gnomad4 AFR exome
AF:
0.000767
Gnomad4 AMR exome
AF:
0.000265
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000530
Gnomad4 SAS exome
AF:
0.000111
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000682
Gnomad4 OTH exome
AF:
0.000142
GnomAD4 genome
AF:
0.0000747
AC:
10
AN:
133892
Hom.:
0
Cov.:
0
AF XY:
0.000125
AC XY:
8
AN XY:
63870
show subpopulations
Gnomad4 AFR
AF:
0.0000286
Gnomad4 AMR
AF:
0.0000759
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000217
Gnomad4 SAS
AF:
0.000247
Gnomad4 FIN
AF:
0.000141
Gnomad4 NFE
AF:
0.0000784
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 04, 2025
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs144131869; hg19: chr1-241663902; API