chr12-132490685-G-T

Variant names:

• chr12-132490685-G-T
• NM_001367871.1:c.115G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001367871.1(FBRSL1):​c.115G>T​(p.Glu39*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FBRSL1 NM_001367871.1 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.241
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 12-132490685-G-T is Benign according to our data. Variant chr12-132490685-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2443335.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRSL1	NM_001367871.1	c.115G>T	p.Glu39*	stop_gained	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.115G>T	p.Glu39*	stop_gained	Exon 1 of 19		NM_001367871.1	ENSP00000505341.1
FBRSL1	ENST00000434748.2	c.115G>T	p.Glu39*	stop_gained	Exon 1 of 17	1		ENSP00000396160.2
FBRSL1	ENST00000650108.1	c.115G>T	p.Glu39*	stop_gained	Exon 1 of 20			ENSP00000496901.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 854592 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 397422

African (AFR) AF: 0.00 AC: 0 AN: 16178

American (AMR) AF: 0.00 AC: 0 AN: 4920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6912

East Asian (EAS) AF: 0.00 AC: 0 AN: 3798

South Asian (SAS) AF: 0.00 AC: 0 AN: 21270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 770342

Other (OTH) AF: 0.00 AC: 0 AN: 28216

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Benign:1

Jul 14, 2015

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.79	D
PhyloP100		0.24
Vest4		0.069
GERP RS		3.5
Mutation Taster		=40/160	disease causing (fs/PTC)

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

Other links and lift over

hg19: chr12-133067271;