16-30668622-G-A

Variant names:

• chr16-30668622-G-A
• rs1567547614
• NM_001105079.3:c.2137G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001105079.3(FBRS):​c.2137G>A​(p.Gly713Ser) variant causes a missense change. 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 pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBRS NM_001105079.3 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.66

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794
• PP5: Variant 16-30668622-G-A is Pathogenic according to our data. Variant chr16-30668622-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 599483.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRS	NM_001105079.3	c.2137G>A	p.Gly713Ser	missense_variant	Exon 16 of 18	ENST00000356166.11	NP_001098549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBRS	ENST00000356166.11	c.2137G>A	p.Gly713Ser	missense_variant	Exon 16 of 18	5	NM_001105079.3	ENSP00000348489.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Short stature Pathogenic:1

Nov 18, 2001

Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.020	D;D
Sift4G	Benign	0.16	T;T
Polyphen		0.97	.;D
Vest4		0.76
MutPred		0.70		.;Gain of glycosylation at G193 (P = 0.045);
MVP		0.16
MPC		1.1
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.56

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: rs1567547614; hg19: chr16-30679943;