1-212858475-AG-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_014053.4(FLVCR1):c.28del(p.Ala10ArgfsTer40) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000763 in 1,441,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Consequence
FLVCR1
NM_014053.4 frameshift
NM_014053.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.725
Genes affected
FLVCR1 (HGNC:24682): (FLVCR choline and heme transporter 1) This gene encodes a member of the major facilitator superfamily of transporter proteins. The encoded protein is a heme transporter that may play a critical role in erythropoiesis by protecting developing erythroid cells from heme toxicity. This gene may play a role in posterior column ataxia with retinitis pigmentosa and the hematological disorder Diamond-Blackfan syndrome. [provided by RefSeq, Jan 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 41 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-212858475-AG-A is Pathogenic according to our data. Variant chr1-212858475-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 1377362.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLVCR1 | NM_014053.4 | c.28del | p.Ala10ArgfsTer40 | frameshift_variant | 1/10 | ENST00000366971.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLVCR1 | ENST00000366971.9 | c.28del | p.Ala10ArgfsTer40 | frameshift_variant | 1/10 | 1 | NM_014053.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000527 AC: 8AN: 151930Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
8
AN:
151930
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000233 AC: 3AN: 1289226Hom.: 0 Cov.: 31 AF XY: 0.00000319 AC XY: 2AN XY: 626032
GnomAD4 exome
AF:
AC:
3
AN:
1289226
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
626032
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000527 AC: 8AN: 151930Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74216
GnomAD4 genome
?
AF:
AC:
8
AN:
151930
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
74216
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala10Argfs*40) in the FLVCR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLVCR1 are known to be pathogenic (PMID: 23591405, 27923065). This variant has not been reported in the literature in individuals affected with FLVCR1-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1377362). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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