Variant 1-93523471-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001164473.3(FNBP1L):c.322C>A(p.Leu108Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,451,376 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FNBP1L
NM_001164473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

Variant links:

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]

FNBP1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2878739).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNBP1L	NM_001164473.3 link	c.322C>A	p.Leu108Met	missense_variant	4/17	ENST00000271234.13	NP_001157945.1	Q5T0N5-1B4DSI7
FNBP1L	NM_001024948.3 link	c.322C>A	p.Leu108Met	missense_variant	4/14		NP_001020119.1	Q5T0N5-4
FNBP1L	NM_017737.5 link	c.322C>A	p.Leu108Met	missense_variant	4/15		NP_060207.2	Q5T0N5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FNBP1L	ENST00000271234.13 link	c.322C>A	p.Leu108Met	missense_variant	4/17	5	NM_001164473.3	ENSP00000271234.7	Q5T0N5-1
FNBP1L	ENST00000260506.12 link	c.322C>A	p.Leu108Met	missense_variant	4/14	1		ENSP00000260506.8	Q5T0N5-4
FNBP1L	ENST00000370253.6 link	c.322C>A	p.Leu108Met	missense_variant	4/15	5		ENSP00000359275.2	Q5T0N5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000213

AC:

AN:

234590

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

126600

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000174

Gnomad SAS exome

AF:

0.0000365

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1451376

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

720902

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000166

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

The c.322C>A (p.L108M) alteration is located in exon 4 (coding exon 4) of the FNBP1L gene. This alteration results from a C to A substitution at nucleotide position 322, causing the leucine (L) at amino acid position 108 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.085

T;.;.;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.2

M;M;.;M

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

N;N;.;N

REVEL

Benign

0.14

Sift

Benign

0.29

T;T;.;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.99, 0.34

.;D;.;B

Vest4

0.37

MutPred

0.56

Gain of disorder (P = 0.0446);Gain of disorder (P = 0.0446);Gain of disorder (P = 0.0446);Gain of disorder (P = 0.0446);

MVP

0.47

MPC

1.1

ClinPred

0.49

GERP RS

5.8

Varity_R

0.21

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over