chr14-75633653-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_017791.3(FLVCR2):c.977C>T(p.Ala326Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
FLVCR2
NM_017791.3 missense
NM_017791.3 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 7.58
Genes affected
FLVCR2 (HGNC:20105): (FLVCR choline and putative heme transporter 2) This gene encodes a member of the major facilitator superfamily. The encoded transmembrane protein is a calcium transporter. Unlike the related protein feline leukemia virus subgroup C receptor 1, the protein encoded by this locus does not bind to feline leukemia virus subgroup C envelope protein. The encoded protein may play a role in development of brain vascular endothelial cells, as mutations at this locus have been associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Aug 2010]
TTLL5 (HGNC:19963): (tubulin tyrosine ligase like 5) This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.865
PP5
Variant 14-75633653-C-T is Pathogenic according to our data. Variant chr14-75633653-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1092.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLVCR2 | NM_017791.3 | c.977C>T | p.Ala326Val | missense_variant | 4/10 | ENST00000238667.9 | NP_060261.2 | |
FLVCR2 | NM_001195283.2 | c.362C>T | p.Ala121Val | missense_variant | 4/10 | NP_001182212.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLVCR2 | ENST00000238667.9 | c.977C>T | p.Ala326Val | missense_variant | 4/10 | 1 | NM_017791.3 | ENSP00000238667 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461712Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727184
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31
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727184
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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EpiCase
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EpiControl
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Fowler syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;T;.;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;T;D;T;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;D;D;T;T;T;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
B;.;.;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at A321 (P = 2e-04);.;.;.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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