16-30667581-C-T

Variant summary

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

The NM_001105079.3(FBRS):​c.2033C>T​(p.Pro678Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,608 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

FBRS
NM_001105079.3 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82
Variant links:
Genes affected
FBRS (HGNC:20442): (fibrosin) Fibrosin is a lymphokine secreted by activated lymphocytes that induces fibroblast proliferation (Prakash and Robbins, 1998 [PubMed 9809749]).[supplied by OMIM, Mar 2008]

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=0.35036296).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBRSNM_001105079.3 linkc.2033C>T p.Pro678Leu missense_variant Exon 15 of 18 ENST00000356166.11 NP_001098549.2 Q9HAH7J3KNZ9B3KTZ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBRSENST00000356166.11 linkc.2033C>T p.Pro678Leu missense_variant Exon 15 of 18 5 NM_001105079.3 ENSP00000348489.5 J3KNZ9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.19e-7
AC:
1
AN:
1390608
Hom.:
0
Cov.:
32
AF XY:
0.00000146
AC XY:
1
AN XY:
685732
show subpopulations
Gnomad4 AFR exome
AF:
0.0000320
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:
0.00
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

not specified Uncertain:1
Dec 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.473C>T (p.P158L) alteration is located in exon 9 (coding exon 8) of the FBRS gene. This alteration results from a C to T substitution at nucleotide position 473, causing the proline (P) at amino acid position 158 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
0.17
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.22
.;T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Benign
0.42
N
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.35
T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.9
.;L
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-6.7
D;D
REVEL
Benign
0.23
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0070
D;D
Polyphen
0.99
.;D
Vest4
0.50
MutPred
0.28
.;Loss of disorder (P = 0.037);
MVP
0.082
MPC
1.1
ClinPred
0.95
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.49
gMVP
0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-30678902; API