Variant 12-132508319-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001367871.1(FBRSL1):c.458C>T(p.Ala153Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,542,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

FBRSL1
NM_001367871.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

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

FBRSL1 links:

FBRSL1 (HGNC:):

FBRSL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBRSL1	NM_001367871.1 linkuse as main transcript	c.458C>T	p.Ala153Val	missense_variant	2/19	ENST00000680143.1	NP_001354800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FBRSL1	ENST00000680143.1 linkuse as main transcript	c.458C>T	p.Ala153Val	missense_variant	2/19		NM_001367871.1	ENSP00000505341.1	A0A7P0Z485
FBRSL1	ENST00000434748.2 linkuse as main transcript	c.458C>T	p.Ala153Val	missense_variant	2/17	1		ENSP00000396160.2	Q9HCM7
FBRSL1	ENST00000650108.1 linkuse as main transcript	c.458C>T	p.Ala153Val	missense_variant	2/20			ENSP00000496901.1	A0A3B3IRR3
FBRSL1	ENST00000542061.2 linkuse as main transcript	c.161C>T	p.Ala54Val	missense_variant	3/4	2		ENSP00000490180.1	A0A1B0GUN3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000349

AC:

AN:

143422

Hom.:

AF XY:

0.0000131

AC XY:

AN XY:

76436

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000128

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:

0.0000371

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000353

AC:

AN:

1389990

Hom.:

Cov.:

AF XY:

0.0000379

AC XY:

AN XY:

685160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000867

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000372

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000433

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.458C>T (p.A153V) alteration is located in exon 2 (coding exon 2) of the FBRSL1 gene. This alteration results from a C to T substitution at nucleotide position 458, causing the alanine (A) at amino acid position 153 to be replaced by a valine (V). 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

0.079

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.22

DEOGEN2

Benign

0.0039

T;.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0097

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.46

N;.;.

REVEL

Benign

0.035

Sift

Benign

0.29

T;.;.

Sift4G

Benign

0.24

T;.;.

Polyphen

0.11

B;.;.

Vest4

0.12

MutPred

0.14

Gain of MoRF binding (P = 0.109);Gain of MoRF binding (P = 0.109);.;

MVP

0.030

ClinPred

0.032

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.081

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.45

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.45

Position offset: -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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over