12-132508219-C-G

Variant names:

• chr12-132508219-C-G
• rs1271488662
• NM_001367871.1:c.358C>G

Variant summary

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

The NM_001367871.1(FBRSL1):​c.358C>G​(p.Arg120Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,878 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: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FBRSL1 NM_001367871.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0700

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=0.19283772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRSL1	NM_001367871.1	c.358C>G	p.Arg120Gly	missense_variant	Exon 2 of 19	ENST00000680143.1	NP_001354800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBRSL1	ENST00000680143.1	c.358C>G	p.Arg120Gly	missense_variant	Exon 2 of 19		NM_001367871.1	ENSP00000505341.1
FBRSL1	ENST00000434748.2	c.358C>G	p.Arg120Gly	missense_variant	Exon 2 of 17	1		ENSP00000396160.2
FBRSL1	ENST00000650108.1	c.358C>G	p.Arg120Gly	missense_variant	Exon 2 of 20			ENSP00000496901.1
FBRSL1	ENST00000542061.2	c.61C>G	p.Arg21Gly	missense_variant	Exon 3 of 4	2		ENSP00000490180.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398878 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689936

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.358C>G (p.R120G) alteration is located in exon 2 (coding exon 2) of the FBRSL1 gene. This alteration results from a C to G substitution at nucleotide position 358, causing the arginine (R) at amino acid position 120 to be replaced by a glycine (G). 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	0.26
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T;.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.050
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.9	D;.;.
REVEL	Benign	0.10
Sift	Benign	0.037	D;.;.
Sift4G	Uncertain	0.050	T;.;.
Polyphen		0.99	D;.;.
Vest4		0.29
MutPred		0.29		Gain of ubiquitination at K118 (P = 0.0212);Gain of ubiquitination at K118 (P = 0.0212);.;
MVP		0.14
ClinPred		0.90	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.31

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

Other links and lift over

dbSNP: rs1271488662; hg19: chr12-133084805;