12-132490664-C-G

Variant names:

• chr12-132490664-C-G
• rs1016361246
• NM_001367871.1:c.94C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367871.1(FBRSL1):​c.94C>G​(p.Pro32Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000401 in 996,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. P32S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: FBRSL1 NM_001367871.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044103563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRSL1	NM_001367871.1	c.94C>G	p.Pro32Ala	missense_variant	Exon 1 of 19	ENST00000680143.1	NP_001354800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBRSL1	ENST00000680143.1	c.94C>G	p.Pro32Ala	missense_variant	Exon 1 of 19		NM_001367871.1	ENSP00000505341.1
FBRSL1	ENST00000434748.2	c.94C>G	p.Pro32Ala	missense_variant	Exon 1 of 17	1		ENSP00000396160.2
FBRSL1	ENST00000650108.1	c.94C>G	p.Pro32Ala	missense_variant	Exon 1 of 20			ENSP00000496901.1

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 145876 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000681

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: 0.00000235 AC: 2 AN: 850646 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 395084

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: 0.00000260

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000137 AC: 2 AN: 145876 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 70976

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000681

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.51
DEOGEN2	Benign	0.0042	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.55	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.020	N;.
REVEL	Benign	0.014
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;.
Polyphen		0.015	B;.
Vest4		0.068
MutPred		0.17		Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP		0.030
ClinPred		0.015	T
GERP RS		2.5
Varity_R		0.028
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

Other links and lift over

dbSNP: rs1016361246; hg19: chr12-133067250;