1-93534817-G-A

Variant names:

• chr1-93534817-G-A
• NM_001164473.3:c.899G>A

Variant summary

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

The NM_001164473.3(FNBP1L):​c.899G>A​(p.Ser300Asn) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNBP1L NM_001164473.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.44

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=0.24894202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP1L	NM_001164473.3	c.899G>A	p.Ser300Asn	missense_variant	Exon 9 of 17	ENST00000271234.13	NP_001157945.1
FNBP1L	NM_001024948.3	c.899G>A	p.Ser300Asn	missense_variant	Exon 9 of 14		NP_001020119.1
FNBP1L	NM_017737.5	c.899G>A	p.Ser300Asn	missense_variant	Exon 9 of 15		NP_060207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNBP1L	ENST00000271234.13	c.899G>A	p.Ser300Asn	missense_variant	Exon 9 of 17	5	NM_001164473.3	ENSP00000271234.7
FNBP1L	ENST00000260506.12	c.899G>A	p.Ser300Asn	missense_variant	Exon 9 of 14	1		ENSP00000260506.8
FNBP1L	ENST00000370253.6	c.899G>A	p.Ser300Asn	missense_variant	Exon 9 of 15	5		ENSP00000359275.2
FNBP1L	ENST00000424449.2	c.434G>A	p.Ser145Asn	missense_variant	Exon 4 of 12	2		ENSP00000397451.2

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

Jan 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.899G>A (p.S300N) alteration is located in exon 9 (coding exon 9) of the FNBP1L gene. This alteration results from a G to A substitution at nucleotide position 899, causing the serine (S) at amino acid position 300 to be replaced by an asparagine (N). 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	0.23
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T;.;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;L;.;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.99	N;N;.;N
REVEL	Benign	0.087
Sift	Benign	0.13	T;T;.;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.95, 0.0010	.;P;.;B
Vest4		0.43
MutPred		0.22		Loss of phosphorylation at S300 (P = 0.0499);Loss of phosphorylation at S300 (P = 0.0499);Loss of phosphorylation at S300 (P = 0.0499);Loss of phosphorylation at S300 (P = 0.0499);
MVP		0.55
MPC		0.87
ClinPred		0.89	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-94000374;