12-132490664-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367871.1(FBRSL1):​c.94C>G​(p.Pro32Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000401 in 996,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P32S) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000014 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000024 ( 0 hom. )

Consequence

FBRSL1
NM_001367871.1 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.698
Variant links:
Genes affected
FBRSL1 (HGNC:29308): (fibrosin like 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.044103563).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBRSL1NM_001367871.1 linkc.94C>G p.Pro32Ala missense_variant Exon 1 of 19 ENST00000680143.1 NP_001354800.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBRSL1ENST00000680143.1 linkc.94C>G p.Pro32Ala missense_variant Exon 1 of 19 NM_001367871.1 ENSP00000505341.1 A0A7P0Z485
FBRSL1ENST00000434748.2 linkc.94C>G p.Pro32Ala missense_variant Exon 1 of 17 1 ENSP00000396160.2 Q9HCM7
FBRSL1ENST00000650108.1 linkc.94C>G p.Pro32Ala missense_variant Exon 1 of 20 ENSP00000496901.1 A0A3B3IRR3

Frequencies

GnomAD3 genomes
AF:
0.0000137
AC:
2
AN:
145876
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000681
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:
0.0000152
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000235
AC:
2
AN:
850646
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
395084
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:
0.00000260
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000137
AC:
2
AN:
145876
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
70976
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000681
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000152
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
15
DANN
Benign
0.51
DEOGEN2
Benign
0.0042
T;.
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.33
N
LIST_S2
Benign
0.55
T;T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.044
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.55
N;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.020
N;.
REVEL
Benign
0.014
Sift
Benign
1.0
T;.
Sift4G
Benign
1.0
T;.
Polyphen
0.015
B;.
Vest4
0.068
MutPred
0.17
Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP
0.030
ClinPred
0.015
T
GERP RS
2.5
Varity_R
0.028
gMVP
0.17

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: rs1016361246; hg19: chr12-133067250; API