Genetic Variant FBRSL1:p.Ala27Asp (chr12-132490650-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367871.1(FBRSL1):c.80C>A(p.Ala27Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. A27V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FBRSL1
NM_001367871.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0850

Publications

0 publications found

Variant links:

Genes affected

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

FBRSL1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
syndromic complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Broad Center for Mendelian Genomics

FBRSL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1402401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRSL1	NM_001367871.1 link	c.80C>A	p.Ala27Asp	missense_variant	Exon 1 of 19	ENST00000680143.1	NP_001354800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBRSL1	ENST00000680143.1 link	c.80C>A	p.Ala27Asp	missense_variant	Exon 1 of 19		NM_001367871.1	ENSP00000505341.1	A0A7P0Z485
FBRSL1	ENST00000434748.2 link	c.80C>A	p.Ala27Asp	missense_variant	Exon 1 of 17	1		ENSP00000396160.2	Q9HCM7
FBRSL1	ENST00000650108.1 link	c.80C>A	p.Ala27Asp	missense_variant	Exon 1 of 20			ENSP00000496901.1	A0A3B3IRR3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

842182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

390098

African (AFR)

AF:

0.00

AC:

AN:

15932

American (AMR)

AF:

0.00

AC:

AN:

2236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5644

East Asian (EAS)

AF:

0.00

AC:

AN:

3738

South Asian (SAS)

AF:

0.00

AC:

AN:

18418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

678

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1664

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

766200

Other (OTH)

AF:

0.00

AC:

AN:

27672

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0057

T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.43

T;T

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.

PhyloP100

-0.085

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.078

Sift

Uncertain

0.015

D;.

Sift4G

Uncertain

0.028

D;.

Polyphen

0.90

P;.

Vest4

0.15

MutPred

0.24

Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);

MVP

0.055

ClinPred

0.28

GERP RS

-1.7

PromoterAI

0.077

Neutral

(source)

Varity_R

0.20

gMVP

0.25

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over