Genetic Variant NM_001367871.1:c.161C>G (chr12-132490731-C-G) – 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.161C>G(p.Pro54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000118 in 844,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P54H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

FBRSL1
NM_001367871.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

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=0.15124163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRSL1	NM_001367871.1 link	c.161C>G	p.Pro54Arg	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.161C>G	p.Pro54Arg	missense_variant	Exon 1 of 19		NM_001367871.1	ENSP00000505341.1	A0A7P0Z485
FBRSL1	ENST00000434748.2 link	c.161C>G	p.Pro54Arg	missense_variant	Exon 1 of 17	1		ENSP00000396160.2	Q9HCM7
FBRSL1	ENST00000650108.1 link	c.161C>G	p.Pro54Arg	missense_variant	Exon 1 of 20			ENSP00000496901.1	A0A3B3IRR3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000118

AC:

AN:

844496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

391372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15972

American (AMR)

AF:

0.00

AC:

AN:

1288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5306

East Asian (EAS)

AF:

0.00

AC:

AN:

4152

South Asian (SAS)

AF:

0.00

AC:

AN:

17338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1632

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

769738

Other (OTH)

AF:

0.0000359

AC:

AN:

27880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.161C>G (p.P54R) alteration is located in exon 1 (coding exon 1) of the FBRSL1 gene. This alteration results from a C to G substitution at nucleotide position 161, causing the proline (P) at amino acid position 54 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.33

T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

PhyloP100

1.2

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.024

Sift

Benign

0.16

T;.

Sift4G

Uncertain

0.035

D;.

Polyphen

0.19

B;.

Vest4

0.16

MutPred

0.28

Gain of MoRF binding (P = 0.0051);Gain of MoRF binding (P = 0.0051);

MVP

0.16

ClinPred

0.35

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.066

gMVP

0.14

Mutation Taster

=92/8

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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NM_001367871.1:c.161C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over