chr1-93534813-A-C

Position:

• chr1-93534813-A-C

Variant summary

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

The NM_001164473.3(FNBP1L):​c.895A>C​(p.Ile299Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNBP1L NM_001164473.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81

Genes affected

FNBP1L (HGNC:20851): (formin binding protein 1 like) The protein encoded by this gene binds to both CDC42 and N-WASP. This protein promotes CDC42-induced actin polymerization by activating the N-WASP-WIP complex and, therefore, is involved in a pathway that links cell surface signals to the actin cytoskeleton. 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=0.18579423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNBP1L	NM_001164473.3	c.895A>C	p.Ile299Leu	missense_variant	9/17	ENST00000271234.13
FNBP1L	NM_001024948.3	c.895A>C	p.Ile299Leu	missense_variant	9/14
FNBP1L	NM_017737.5	c.895A>C	p.Ile299Leu	missense_variant	9/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNBP1L	ENST00000271234.13	c.895A>C	p.Ile299Leu	missense_variant	9/17	5	NM_001164473.3
FNBP1L	ENST00000260506.12	c.895A>C	p.Ile299Leu	missense_variant	9/14	1		P4
FNBP1L	ENST00000370253.6	c.895A>C	p.Ile299Leu	missense_variant	9/15	5		A1
FNBP1L	ENST00000424449.2	c.433A>C	p.Ile145Leu	missense_variant	4/12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jul 20, 2022

The c.895A>C (p.I299L) alteration is located in exon 9 (coding exon 9) of the FNBP1L gene. This alteration results from a A to C substitution at nucleotide position 895, causing the isoleucine (I) at amino acid position 299 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	0.12
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.024	T;.;.;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.18	N;N;.;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.72	N;N;.;N
REVEL	Benign	0.21
Sift	Benign	1.0	T;T;.;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.99, 0.0020	.;D;.;B
Vest4		0.37
MutPred		0.27		Gain of catalytic residue at I299 (P = 0.1208);Gain of catalytic residue at I299 (P = 0.1208);Gain of catalytic residue at I299 (P = 0.1208);Gain of catalytic residue at I299 (P = 0.1208);
MVP		0.62
MPC		0.37
ClinPred		0.77	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.36

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: chr1-94000370;