Variant 1-241500602-TGAGAGAGAGAGAGAGAGA-TGAGAGAGAGAGAGAGAGAGAGAGAGAGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_000143.4(FH):c.1237-22_1237-13dupTCTCTCTCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.040 ( 148 hom., cov: 0)

Exomes 𝑓: 0.029 ( 165 hom. )

Failed GnomAD Quality Control

Consequence

FH
NM_000143.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:3

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]

FH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 1-241500602-T-TGAGAGAGAGA is Benign according to our data. Variant chr1-241500602-T-TGAGAGAGAGA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 296869.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Benign=2, Likely_benign=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FH	NM_000143.4 link	c.1237-22_1237-13dupTCTCTCTCTC		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
FH	ENST00000366560.4 link	c.1237-22_1237-13dupTCTCTCTCTC		intron_variant	Intron 8 of 9	1	NM_000143.4	ENSP00000355518.4		P07954-1

Frequencies

GnomAD3 genomes

AF:

0.0401

AC:

5350

AN:

133524

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0573

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0296

Gnomad ASJ

AF:

0.0180

Gnomad EAS

AF:

0.0350

Gnomad SAS

AF:

0.0623

Gnomad FIN

AF:

0.0339

Gnomad MID

AF:

0.0455

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0372

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0286

AC:

38329

AN:

1341810

Hom.:

165

Cov.:

AF XY:

0.0286

AC XY:

19076

AN XY:

667912

show subpopulations

Gnomad4 AFR exome

AF:

0.0419

Gnomad4 AMR exome

AF:

0.0147

Gnomad4 ASJ exome

AF:

0.0141

Gnomad4 EAS exome

AF:

0.0177

Gnomad4 SAS exome

AF:

0.0380

Gnomad4 FIN exome

AF:

0.0212

Gnomad4 NFE exome

AF:

0.0290

Gnomad4 OTH exome

AF:

0.0294

GnomAD4 genome

AF:

0.0401

AC:

5356

AN:

133612

Hom.:

148

Cov.:

AF XY:

0.0405

AC XY:

2584

AN XY:

63738

show subpopulations

Gnomad4 AFR

AF:

0.0574

Gnomad4 AMR

AF:

0.0294

Gnomad4 ASJ

AF:

0.0180

Gnomad4 EAS

AF:

0.0348

Gnomad4 SAS

AF:

0.0625

Gnomad4 FIN

AF:

0.0339

Gnomad4 NFE

AF:

0.0342

Gnomad4 OTH

AF:

0.0373

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary leiomyomatosis and renal cell cancer

Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fumarase deficiency

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over