1-241500602-TGAGAGAGAGAGAGAGAGA-TGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000143.4(FH):​c.1237-32_1237-13dupTCTCTCTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 0)
Exomes 𝑓: 0.00040 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

FH
NM_000143.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.993
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 -16 ACMG points.

BP6
Variant 1-241500602-T-TGAGAGAGAGAGAGAGAGAGA is Benign according to our data. Variant chr1-241500602-T-TGAGAGAGAGAGAGAGAGAGA is described in ClinVar as [Likely_benign]. Clinvar id is 1692240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00177 (237/133868) while in subpopulation AFR AF= 0.00383 (134/34954). AF 95% confidence interval is 0.00331. There are 3 homozygotes in gnomad4. There are 108 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 237 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FHNM_000143.4 linkc.1237-32_1237-13dupTCTCTCTCTCTCTCTCTCTC intron_variant ENST00000366560.4 NP_000134.2 P07954-1A0A0S2Z4C3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FHENST00000366560.4 linkc.1237-32_1237-13dupTCTCTCTCTCTCTCTCTCTC intron_variant 1 NM_000143.4 ENSP00000355518.4 P07954-1

Frequencies

GnomAD3 genomes
AF:
0.00177
AC:
237
AN:
133778
Hom.:
3
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00385
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000228
Gnomad ASJ
AF:
0.00153
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000246
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00694
Gnomad NFE
AF:
0.00141
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000398
AC:
540
AN:
1356380
Hom.:
0
Cov.:
48
AF XY:
0.000379
AC XY:
256
AN XY:
675240
show subpopulations
Gnomad4 AFR exome
AF:
0.00112
Gnomad4 AMR exome
AF:
0.000193
Gnomad4 ASJ exome
AF:
0.000982
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000161
Gnomad4 FIN exome
AF:
0.000226
Gnomad4 NFE exome
AF:
0.000405
Gnomad4 OTH exome
AF:
0.000515
GnomAD4 genome
AF:
0.00177
AC:
237
AN:
133868
Hom.:
3
Cov.:
0
AF XY:
0.00169
AC XY:
108
AN XY:
63858
show subpopulations
Gnomad4 AFR
AF:
0.00383
Gnomad4 AMR
AF:
0.000228
Gnomad4 ASJ
AF:
0.00153
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000247
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.00141
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingCenter for Genomic Medicine, Rigshospitalet, Copenhagen University HospitalMar 04, 2025- -
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submittercurationSema4, Sema4Mar 14, 2021- -

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