3-133400306-C-T

Variant summary

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

The NM_003571.4(BFSP2):​c.223C>T​(p.Arg75Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,670 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R75H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BFSP2
NM_003571.4 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.26
Variant links:
Genes affected
BFSP2 (HGNC:1041): (beaded filament structural protein 2) More than 99% of the vertebrate ocular lens is comprised of terminally differentiated lens fiber cells. Two lens-specific intermediate filament-like proteins, the protein product of this gene (phakinin), and filensin, are expressed only after fiber cell differentiation has begun. Both proteins are found in a structurally unique cytoskeletal element that is referred to as the beaded filament (BF). Mutations in this gene have been associated with juvenile-onset, progressive cataracts and Dowling-Meara epidermolysis bullosa simplex. [provided by RefSeq, Jun 2009]

Genome browser will be placed here

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=0.30351228).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BFSP2NM_003571.4 linkc.223C>T p.Arg75Cys missense_variant Exon 1 of 7 ENST00000302334.3 NP_003562.1 Q13515
BFSP2XM_017007315.2 linkc.223C>T p.Arg75Cys missense_variant Exon 1 of 6 XP_016862804.1 Q13515

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BFSP2ENST00000302334.3 linkc.223C>T p.Arg75Cys missense_variant Exon 1 of 7 1 NM_003571.4 ENSP00000304987.2 Q13515
BFSP2ENST00000513441.1 linkn.233C>T non_coding_transcript_exon_variant Exon 1 of 2 5
BFSP2ENST00000511140.1 linkn.-156C>T upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461670
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727128
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.223C>T (p.R75C) alteration is located in exon 1 (coding exon 1) of the BFSP2 gene. This alteration results from a C to T substitution at nucleotide position 223, causing the arginine (R) at amino acid position 75 to be replaced by a cysteine (C). 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
0.13
BayesDel_addAF
Uncertain
0.022
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.074
D
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.30
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-2.5
D
REVEL
Uncertain
0.41
Sift
Benign
0.075
T
Sift4G
Pathogenic
0.0010
D
Polyphen
0.56
P
Vest4
0.40
MutPred
0.58
Loss of MoRF binding (P = 0.0061);
MVP
0.82
MPC
0.24
ClinPred
0.94
D
GERP RS
4.1
Varity_R
0.13
gMVP
0.56

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: rs766843026; hg19: chr3-133119150; API