rs10927851

chr1-15770439-C-Gchr1-15770439-C-T

Variant summary

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

The NM_017556.4(FBLIM1):c.572C>G(p.Ser191Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. S191F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 28)
• Consequence: FBLIM1 NM_017556.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

Genes affected

FBLIM1 (HGNC:24686): (filamin binding LIM protein 1) This gene encodes a protein with an N-terminal filamin-binding domain, a central proline-rich domain, and, multiple C-terminal LIM domains. This protein localizes at cell junctions and may link cell adhesion structures to the actin cytoskeleton. This protein may be involved in the assembly and stabilization of actin-filaments and likely plays a role in modulating cell adhesion, cell morphology and cell motility. This protein also localizes to the nucleus and may affect cardiomyocyte differentiation after binding with the CSX/NKX2-5 transcription factor. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 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=0.26969594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLIM1	NM_017556.4	c.572C>G	p.Ser191Cys	missense_variant	6/9	ENST00000375766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLIM1	ENST00000375766.8	c.572C>G	p.Ser191Cys	missense_variant	6/9	2	NM_017556.4	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	24
Dann	Benign	0.97
DEOGEN2	Benign	0.35	T;T;D;.;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.6	L;L;.;L;.
MutationTaster	Benign	0.92	D;D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.0	N;N;D;N;N
REVEL	Benign	0.056
Sift	Benign	0.23	T;T;T;T;T
Sift4G	Benign	0.073	T;T;D;D;T
Polyphen		0.079	B;B;.;B;B
Vest4		0.28
MutPred		0.35		Loss of glycosylation at T189 (P = 0.04);Loss of glycosylation at T189 (P = 0.04);.;Loss of glycosylation at T189 (P = 0.04);.;
MVP		0.55
MPC		0.82
ClinPred		0.80	D
GERP RS		5.2
Varity_R		0.25
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

LitVar

Other links and lift over

dbSNP: rs10927851; hg19: chr1-16096934;