rs118204040
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_000140.5(FECH):āc.1085T>Gā(p.Val362Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,352 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
FECH
NM_000140.5 missense
NM_000140.5 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 2.70
Genes affected
FECH (HGNC:3647): (ferrochelatase) The protein encoded by this gene is localized to the mitochondrion, where it catalyzes the insertion of the ferrous form of iron into protoporphyrin IX in the heme synthesis pathway. Mutations in this gene are associated with erythropoietic protoporphyria. Two transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome 3.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 18-57551367-A-C is Pathogenic according to our data. Variant chr18-57551367-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 554.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FECH | NM_000140.5 | c.1085T>G | p.Val362Gly | missense_variant | 10/11 | ENST00000262093.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FECH | ENST00000262093.11 | c.1085T>G | p.Val362Gly | missense_variant | 10/11 | 1 | NM_000140.5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460352Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726582
GnomAD4 exome
AF:
AC:
2
AN:
1460352
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
726582
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Protoporphyria, erythropoietic, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 04, 1994 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
A;A
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Gain of disorder (P = 0.0154);.;
MVP
MPC
1.1
ClinPred
D
GERP RS
Varity_R
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