16-30667581-C-T

Variant names:

• chr16-30667581-C-T
• NM_001105079.3:c.2033C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001105079.3(FBRS):​c.2033C>T​(p.Pro678Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,608 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FBRS NM_001105079.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82

Genes affected

FBRS (HGNC:20442): (fibrosin) Fibrosin is a lymphokine secreted by activated lymphocytes that induces fibroblast proliferation (Prakash and Robbins, 1998 [PubMed 9809749]).[supplied by OMIM, Mar 2008]

ACMG classification

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=0.35036296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRS	NM_001105079.3	c.2033C>T	p.Pro678Leu	missense_variant	Exon 15 of 18	ENST00000356166.11	NP_001098549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBRS	ENST00000356166.11	c.2033C>T	p.Pro678Leu	missense_variant	Exon 15 of 18	5	NM_001105079.3	ENSP00000348489.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390608 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 685732

Gnomad4 AFR exome AF: 0.0000320

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473C>T (p.P158L) alteration is located in exon 9 (coding exon 8) of the FBRS gene. This alteration results from a C to T substitution at nucleotide position 473, causing the proline (P) at amino acid position 158 to be replaced by a leucine (L). 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	0.17
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-6.7	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.99	.;D
Vest4		0.50
MutPred		0.28		.;Loss of disorder (P = 0.037);
MVP		0.082
MPC		1.1
ClinPred		0.95	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
gMVP		0.45

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: chr16-30678902;