dbSNP rs377213746: FBRSL1:p.Pro127Thr (chr12-132508240-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001367871.1(FBRSL1):c.379C>A(p.Pro127Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000903 in 1,550,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. P127A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

FBRSL1
NM_001367871.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.38

Variant links:

Genes affected

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

FBRSL1 links:

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=0.03449166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRSL1	NM_001367871.1 link	c.379C>A	p.Pro127Thr	missense_variant	Exon 2 of 19	ENST00000680143.1	NP_001354800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBRSL1	ENST00000680143.1 link	c.379C>A	p.Pro127Thr	missense_variant	Exon 2 of 19		NM_001367871.1	ENSP00000505341.1	A0A7P0Z485
FBRSL1	ENST00000434748.2 link	c.379C>A	p.Pro127Thr	missense_variant	Exon 2 of 17	1		ENSP00000396160.2	Q9HCM7
FBRSL1	ENST00000650108.1 link	c.379C>A	p.Pro127Thr	missense_variant	Exon 2 of 20			ENSP00000496901.1	A0A3B3IRR3
FBRSL1	ENST00000542061.2 link	c.82C>A	p.Pro28Thr	missense_variant	Exon 3 of 4	2		ENSP00000490180.1	A0A1B0GUN3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1398706

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

689864

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000839

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000556

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.083

DANN

Benign

0.63

DEOGEN2

Benign

0.00019

T;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

0.18

N;.;.

REVEL

Benign

0.0060

Sift

Benign

1.0

T;.;.

Sift4G

Benign

1.0

T;.;.

Polyphen

0.0090

B;.;.

Vest4

0.045

MutPred

0.26

Gain of phosphorylation at P127 (P = 0.0065);Gain of phosphorylation at P127 (P = 0.0065);.;

MVP

0.014

ClinPred

0.048

GERP RS

-5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.016

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over