12-132490728-C-A

Position:

• chr12-132490728-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367871.1(FBRSL1):​c.158C>A​(p.Pro53His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 840,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: FBRSL1 NM_001367871.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.187

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.109812796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBRSL1	NM_001367871.1	c.158C>A	p.Pro53His	missense_variant	1/19	ENST00000680143.1	NP_001354800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBRSL1	ENST00000680143.1	c.158C>A	p.Pro53His	missense_variant	1/19		NM_001367871.1	ENSP00000505341	A2
FBRSL1	ENST00000434748.2	c.158C>A	p.Pro53His	missense_variant	1/17	1		ENSP00000396160	P2
FBRSL1	ENST00000650108.1	c.158C>A	p.Pro53His	missense_variant	1/20			ENSP00000496901	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000119 AC: 10 AN: 840468 Hom.: 0 Cov.: 28 AF XY: 0.0000129 AC XY: 5 AN XY: 388936

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: 0.000173

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000913

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.158C>A (p.P53H) alteration is located in exon 1 (coding exon 1) of the FBRSL1 gene. This alteration results from a C to A substitution at nucleotide position 158, causing the proline (P) at amino acid position 53 to be replaced by a histidine (H). 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	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0066	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.30	T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	D;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N;.
REVEL	Benign	0.012
Sift	Uncertain	0.014	D;.
Sift4G	Uncertain	0.045	D;.
Polyphen		0.025	B;.
Vest4		0.24
MutPred		0.24		Gain of MoRF binding (P = 0.0436);Gain of MoRF binding (P = 0.0436);
MVP		0.13
ClinPred		0.28	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-133067314;