16-30668608-A-C

Variant names:

• chr16-30668608-A-C
• rs1326344575
• NM_001105079.3:c.2123A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP2 BP4

The NM_001105079.3(FBRS):​c.2123A>C​(p.Asn708Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/21 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. N708S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000082 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FBRS NM_001105079.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59
• Publications: 1 publications found

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

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

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.76428 (below the threshold of 3.09). Trascript score misZ: -2.0176 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.27490383).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105079.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBRS	NM_001105079.3	MANE Select	c.2123A>C	p.Asn708Thr	missense	Exon 16 of 18	NP_001098549.2	J3KNZ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBRS	ENST00000356166.11	TSL:5 MANE Select	c.2123A>C	p.Asn708Thr	missense	Exon 16 of 18	ENSP00000348489.5	J3KNZ9
	FBRS	ENST00000287468.5	TSL:5	c.563A>C	p.Asn188Thr	missense	Exon 10 of 12	ENSP00000287468.5	Q9HAH7-2
	FBRS	ENST00000494101.1	TSL:2	n.670A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0000822 AC: 12 AN: 145968 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000675

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000440

Gnomad SAS AF: 0.000237

Gnomad FIN AF: 0.000322

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000758

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1418552 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705554

African (AFR) AF: 0.00 AC: 0 AN: 32160

American (AMR) AF: 0.00 AC: 0 AN: 43446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24610

East Asian (EAS) AF: 0.00 AC: 0 AN: 35424

South Asian (SAS) AF: 0.00 AC: 0 AN: 85828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085336

Other (OTH) AF: 0.00 AC: 0 AN: 57572

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000821 AC: 12 AN: 146102 Hom.: 0 Cov.: 32 AF XY: 0.0000843 AC XY: 6 AN XY: 71214

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40580

American (AMR) AF: 0.0000674 AC: 1 AN: 14836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.000441 AC: 2 AN: 4536

South Asian (SAS) AF: 0.000236 AC: 1 AN: 4230

European-Finnish (FIN) AF: 0.000322 AC: 3 AN: 9324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000758 AC: 5 AN: 65974

Other (OTH) AF: 0.00 AC: 0 AN: 2062

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		5.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.099
Sift	Benign	0.13	T
Sift4G	Uncertain	0.022	D
Polyphen		0.96	D
Vest4		0.60
MutPred		0.13		Gain of phosphorylation at N188 (P = 0.0571)
MVP		0.043
MPC		0.96
ClinPred		0.77	D
GERP RS		5.0
Varity_R		0.17
gMVP		0.24

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

dbSNP: rs1326344575; hg19: chr16-30679929;