Variant 12-132490616-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001367871.1(FBRSL1):c.46G>A(p.Asp16Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000234 in 983,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

FBRSL1
NM_001367871.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Variant links:

Genes affected

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

FBRSL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26497674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBRSL1	NM_001367871.1 linkuse as main transcript	c.46G>A	p.Asp16Asn	missense_variant	1/19	ENST00000680143.1	NP_001354800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FBRSL1	ENST00000680143.1 linkuse as main transcript	c.46G>A	p.Asp16Asn	missense_variant	1/19		NM_001367871.1	ENSP00000505341	A2
FBRSL1	ENST00000434748.2 linkuse as main transcript	c.46G>A	p.Asp16Asn	missense_variant	1/17	1		ENSP00000396160	P2
FBRSL1	ENST00000650108.1 linkuse as main transcript	c.46G>A	p.Asp16Asn	missense_variant	1/20			ENSP00000496901	A2

Frequencies

GnomAD3 genomes

AF:

0.0000205

AC:

AN:

146154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000491

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:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

837230

Hom.:

Cov.:

AF XY:

0.0000258

AC XY:

AN XY:

387142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000235

Gnomad4 OTH exome

AF:

0.0000728

GnomAD4 genome

AF:

0.0000205

AC:

AN:

146154

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

71072

show subpopulations

Gnomad4 AFR

AF:

0.0000491

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:

0.0000152

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

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

Jan 09, 2024

The c.46G>A (p.D16N) alteration is located in exon 1 (coding exon 1) of the FBRSL1 gene. This alteration results from a G to A substitution at nucleotide position 46, causing the aspartic acid (D) at amino acid position 16 to be replaced by an asparagine (N). 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

Pathogenic

0.80

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.0048

T;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.81

T;T

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.78

N;.

REVEL

Benign

0.11

Sift

Benign

0.12

T;.

Sift4G

Benign

0.14

T;.

Polyphen

0.99

D;.

Vest4

0.10

MutPred

0.25

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.048

ClinPred

0.51

GERP RS

3.4

Varity_R

0.15

gMVP

0.17

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over