chr14-75635007-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017791.3(FLVCR2):ā€‹c.1118C>Gā€‹(p.Thr373Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,451,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

FLVCR2
NM_017791.3 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79
Variant links:
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39526382).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FLVCR2NM_017791.3 linkuse as main transcriptc.1118C>G p.Thr373Ser missense_variant 5/10 ENST00000238667.9 NP_060261.2
FLVCR2NM_001195283.2 linkuse as main transcriptc.503C>G p.Thr168Ser missense_variant 5/10 NP_001182212.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FLVCR2ENST00000238667.9 linkuse as main transcriptc.1118C>G p.Thr373Ser missense_variant 5/101 NM_017791.3 ENSP00000238667 P1Q9UPI3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251074
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135686
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1451476
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
722852
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 04, 2022The c.1118C>G (p.T373S) alteration is located in exon 5 (coding exon 5) of the FLVCR2 gene. This alteration results from a C to G substitution at nucleotide position 1118, causing the threonine (T) at amino acid position 373 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.091
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.;.;.;T;T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.89
D;D;D;D;D;D
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.40
T;T;T;T;T;T
MetaSVM
Uncertain
0.073
D
MutationAssessor
Uncertain
2.3
M;.;.;.;.;.
MutationTaster
Benign
0.97
D;D;D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.9
D;D;D;D;D;D
REVEL
Benign
0.27
Sift
Benign
0.12
T;T;T;T;T;T
Sift4G
Benign
0.15
T;T;T;T;T;D
Polyphen
0.42
B;.;.;.;.;.
Vest4
0.67
MutPred
0.34
Gain of catalytic residue at L368 (P = 0.007);.;.;.;.;.;
MVP
0.88
MPC
0.38
ClinPred
0.74
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.70
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs369882008; hg19: chr14-76101350; API