chr1-15765167-C-T

Position:

• chr1-15765167-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017556.4(FBLIM1):​c.184C>T​(p.Pro62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBLIM1 NM_017556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.133

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068742424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLIM1	NM_017556.4	c.184C>T	p.Pro62Ser	missense_variant	3/9	ENST00000375766.8	NP_060026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLIM1	ENST00000375766.8	c.184C>T	p.Pro62Ser	missense_variant	3/9	2	NM_017556.4	ENSP00000364921.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.184C>T (p.P62S) alteration is located in exon 2 (coding exon 1) of the FBLIM1 gene. This alteration results from a C to T substitution at nucleotide position 184, causing the proline (P) at amino acid position 62 to be replaced by a serine (S). 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	0.072
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	3.1
DANN	Benign	0.25
DEOGEN2	Benign	0.071	T;T;T;T;T;.;.;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.65	T;.;T;T;T;T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.069	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	.;N;N;.;.;.;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.5	D;N;N;D;N;D;N;N
REVEL	Benign	0.085
Sift	Benign	0.38	T;T;T;T;T;T;T;T
Sift4G	Benign	0.77	T;T;T;T;T;T;T;T
Polyphen		0.0010, 0.049, 0.0	.;B;B;.;.;.;B;B
Vest4		0.054, 0.057, 0.052, 0.065
MutPred		0.16		Gain of phosphorylation at P62 (P = 0.0199);Gain of phosphorylation at P62 (P = 0.0199);Gain of phosphorylation at P62 (P = 0.0199);Gain of phosphorylation at P62 (P = 0.0199);Gain of phosphorylation at P62 (P = 0.0199);Gain of phosphorylation at P62 (P = 0.0199);Gain of phosphorylation at P62 (P = 0.0199);Gain of phosphorylation at P62 (P = 0.0199);
MVP		0.58
MPC		0.25
ClinPred		0.035	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.15

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: rs2068857728; hg19: chr1-16091662;