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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367871.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBRSL1	NM_001367871.1	MANE Select	c.80C>A	p.Ala27Asp	missense	Exon 1 of 19	NP_001354800.1	A0A7P0Z485
FBRSL1	NM_001142641.2		c.80C>A	p.Ala27Asp	missense	Exon 1 of 17	NP_001136113.1	Q9HCM7
FBRSL1	NM_001382739.1		c.80C>A	p.Ala27Asp	missense	Exon 1 of 19	NP_001369668.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBRSL1	ENST00000680143.1	MANE Select	c.80C>A	p.Ala27Asp	missense	Exon 1 of 19	ENSP00000505341.1	A0A7P0Z485
FBRSL1	ENST00000434748.2	TSL:1	c.80C>A	p.Ala27Asp	missense	Exon 1 of 17	ENSP00000396160.2	Q9HCM7
FBRSL1	ENST00000955044.1		c.80C>A	p.Ala27Asp	missense	Exon 1 of 20	ENSP00000625103.1

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 v4.9

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

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-0.085

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.1

REVEL

Benign

0.078

Sift

Uncertain

0.015

Sift4G

Uncertain

0.028

Polyphen

0.90

Vest4

0.15

MutPred

0.24

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over