Variant 1-93533024-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001164473.3(FNBP1L):c.742T>G(p.Leu248Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FNBP1L
NM_001164473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNBP1L	NM_001164473.3 linkuse as main transcript	c.742T>G	p.Leu248Val	missense_variant	8/17	ENST00000271234.13	NP_001157945.1	Q5T0N5-1B4DSI7
FNBP1L	NM_001024948.3 linkuse as main transcript	c.742T>G	p.Leu248Val	missense_variant	8/14		NP_001020119.1	Q5T0N5-4
FNBP1L	NM_017737.5 linkuse as main transcript	c.742T>G	p.Leu248Val	missense_variant	8/15		NP_060207.2	Q5T0N5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FNBP1L	ENST00000271234.13 linkuse as main transcript	c.742T>G	p.Leu248Val	missense_variant	8/17	5	NM_001164473.3	ENSP00000271234.7	Q5T0N5-1
FNBP1L	ENST00000260506.12 linkuse as main transcript	c.742T>G	p.Leu248Val	missense_variant	8/14	1		ENSP00000260506.8	Q5T0N5-4
FNBP1L	ENST00000370253.6 linkuse as main transcript	c.742T>G	p.Leu248Val	missense_variant	8/15	5		ENSP00000359275.2	Q5T0N5-3
FNBP1L	ENST00000424449.2 linkuse as main transcript	c.277T>G	p.Leu93Val	missense_variant	3/12	2		ENSP00000397451.2	A0A075B6Q2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726738

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Sep 04, 2024

The c.742T>G (p.L248V) alteration is located in exon 8 (coding exon 8) of the FNBP1L gene. This alteration results from a T to G substitution at nucleotide position 742, causing the leucine (L) at amino acid position 248 to be replaced by a valine (V). 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

Uncertain

0.55

BayesDel_addAF

Benign

0.0041

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.;.;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.83

D;D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.0

M;M;.;M

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.6

D;D;.;D

REVEL

Benign

0.28

Sift

Uncertain

0.0020

D;D;.;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

0.99, 0.98

.;D;.;D

Vest4

0.81

MutPred

0.76

Gain of ubiquitination at K246 (P = 0.1047);Gain of ubiquitination at K246 (P = 0.1047);Gain of ubiquitination at K246 (P = 0.1047);Gain of ubiquitination at K246 (P = 0.1047);

MVP

0.46

MPC

1.0

ClinPred

0.99

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.81

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

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