14-75579082-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017791.3(FLVCR2):​c.110C>T​(p.Pro37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FLVCR2
NM_017791.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.547
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]
FLVCR2-AS1 (HGNC:55854): (FLVCR2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1737211).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLVCR2NM_017791.3 linkc.110C>T p.Pro37Leu missense_variant Exon 1 of 10 ENST00000238667.9 NP_060261.2 Q9UPI3-1
FLVCR2-AS1NR_110552.1 linkn.507G>A non_coding_transcript_exon_variant Exon 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLVCR2ENST00000238667.9 linkc.110C>T p.Pro37Leu missense_variant Exon 1 of 10 1 NM_017791.3 ENSP00000238667.4 Q9UPI3-1
FLVCR2-AS1ENST00000455232.1 linkn.507G>A non_coding_transcript_exon_variant Exon 1 of 3 1
FLVCR2-AS1ENST00000693551.1 linkn.571G>A non_coding_transcript_exon_variant Exon 1 of 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251398
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461814
Hom.:
0
Cov.:
37
AF XY:
0.00000413
AC XY:
3
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Feb 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.110C>T (p.P37L) alteration is located in exon 1 (coding exon 1) of the FLVCR2 gene. This alteration results from a C to T substitution at nucleotide position 110, causing the proline (P) at amino acid position 37 to be replaced by a leucine (L). 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
0.12
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.027
Eigen_PC
Benign
-0.060
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.030
N
REVEL
Benign
0.042
Sift
Uncertain
0.0060
D
Sift4G
Benign
0.10
T
Polyphen
0.90
P
Vest4
0.20
MutPred
0.31
Gain of catalytic residue at V35 (P = 2e-04);
MVP
0.62
MPC
0.96
ClinPred
0.78
D
GERP RS
3.2
Varity_R
0.074
gMVP
0.41

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: rs763845250; hg19: chr14-76045425; API