1-241500602-TGAGAGAGAGAGAGAGAGA-TGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000143.4(FH):​c.1237-36_1237-13dupTCTCTCTCTCTCTCTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00019 ( 1 hom., cov: 0)
Exomes 𝑓: 0.000013 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

FH
NM_000143.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FHNM_000143.4 linkc.1237-36_1237-13dupTCTCTCTCTCTCTCTCTCTCTCTC 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.1237-36_1237-13dupTCTCTCTCTCTCTCTCTCTCTCTC intron_variant Intron 8 of 9 1 NM_000143.4 ENSP00000355518.4 P07954-1

Frequencies

GnomAD3 genomes
AF:
0.000194
AC:
26
AN:
133796
Hom.:
1
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000344
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000204
Gnomad OTH
AF:
0.000562
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000133
AC:
18
AN:
1356812
Hom.:
0
Cov.:
48
AF XY:
0.0000163
AC XY:
11
AN XY:
675466
show subpopulations
Gnomad4 AFR exome
AF:
0.0000959
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:
0.0000251
Gnomad4 NFE exome
AF:
0.0000125
Gnomad4 OTH exome
AF:
0.0000178
GnomAD4 genome
AF:
0.000194
AC:
26
AN:
133886
Hom.:
1
Cov.:
0
AF XY:
0.000188
AC XY:
12
AN XY:
63868
show subpopulations
Gnomad4 AFR
AF:
0.000343
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000204
Gnomad4 OTH
AF:
0.000556

ClinVar

Not reported in ClinVar

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