16-30667369-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001105079.3(FBRS):​c.1925C>T​(p.Pro642Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000154 in 1,553,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

FBRS
NM_001105079.3 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00
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 Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.75
BS2
High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBRSNM_001105079.3 linkc.1925C>T p.Pro642Leu missense_variant Exon 14 of 18 ENST00000356166.11 NP_001098549.2 Q9HAH7J3KNZ9B3KTZ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBRSENST00000356166.11 linkc.1925C>T p.Pro642Leu missense_variant Exon 14 of 18 5 NM_001105079.3 ENSP00000348489.5 J3KNZ9

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000186
AC:
3
AN:
161212
Hom.:
0
AF XY:
0.0000117
AC XY:
1
AN XY:
85154
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000800
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:
0.0000158
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
21
AN:
1401626
Hom.:
0
Cov.:
32
AF XY:
0.0000159
AC XY:
11
AN XY:
691568
show subpopulations
Gnomad4 AFR exome
AF:
0.0000631
Gnomad4 AMR exome
AF:
0.0000556
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000556
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000202
Gnomad4 NFE exome
AF:
0.0000120
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000989
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000186
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.365C>T (p.P122L) alteration is located in exon 8 (coding exon 7) of the FBRS gene. This alteration results from a C to T substitution at nucleotide position 365, causing the proline (P) at amino acid position 122 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
0.31
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
.;T
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.055
D
MetaRNN
Pathogenic
0.75
D;D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Uncertain
2.6
.;M
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-6.5
D;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0010
D;D
Sift4G
Benign
0.063
T;D
Polyphen
1.0
.;D
Vest4
0.80
MVP
0.24
MPC
1.1
ClinPred
0.92
D
GERP RS
5.1
Varity_R
0.70
gMVP
0.59

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: rs754944022; hg19: chr16-30678690; COSMIC: COSV105153928; COSMIC: COSV105153928; API