rs758077058

Variant summary

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

The NM_001195.5(BFSP1):​c.1738G>A​(p.Ala580Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

BFSP1
NM_001195.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98
Variant links:
Genes affected
BFSP1 (HGNC:1040): (beaded filament structural protein 1) This gene encodes a lens-specific intermediate filament-like protein named filensin. The encoded protein is expressed in lens fiber cells after differentiation has begun. This protein functions as a component of the beaded filament which is a cytoskeletal structure found in lens fiber cells. Mutations in this gene are the cause of autosomal recessive cortical juvenile-onset cataract. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

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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=0.084994584).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BFSP1NM_001195.5 linkc.1738G>A p.Ala580Thr missense_variant Exon 8 of 8 ENST00000377873.8 NP_001186.1 Q12934-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BFSP1ENST00000377873.8 linkc.1738G>A p.Ala580Thr missense_variant Exon 8 of 8 1 NM_001195.5 ENSP00000367104.3 Q12934-1
BFSP1ENST00000377868.6 linkc.1363G>A p.Ala455Thr missense_variant Exon 8 of 8 1 ENSP00000367099.2 Q12934-2
BFSP1ENST00000536626.7 linkc.1321G>A p.Ala441Thr missense_variant Exon 9 of 9 2 ENSP00000442522.1 Q12934-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251458
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461818
Hom.:
0
Cov.:
49
AF XY:
0.00000550
AC XY:
4
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00
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

Inborn genetic diseases Uncertain:1
Oct 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1738G>A (p.A580T) alteration is located in exon 8 (coding exon 8) of the BFSP1 gene. This alteration results from a G to A substitution at nucleotide position 1738, causing the alanine (A) at amino acid position 580 to be replaced by a threonine (T). 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
0.070
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
12
DANN
Benign
0.96
DEOGEN2
Benign
0.078
T;.;.
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.47
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.58
T;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.085
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N;.;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.36
N;N;N
REVEL
Benign
0.027
Sift
Benign
0.21
T;T;T
Sift4G
Benign
0.51
T;.;T
Polyphen
0.47
P;B;.
Vest4
0.13
MutPred
0.17
Gain of phosphorylation at A580 (P = 0.0021);.;.;
MVP
0.37
MPC
0.086
ClinPred
0.13
T
GERP RS
2.5
Varity_R
0.028
gMVP
0.098

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: rs758077058; hg19: chr20-17474979; API