Variant 1-93522104-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164473.3(FNBP1L):c.163C>G(p.Pro55Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000729 in 1,371,238 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

FNBP1L
NM_001164473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.61

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNBP1L	NM_001164473.3 linkuse as main transcript	c.163C>G	p.Pro55Ala	missense_variant	3/17	ENST00000271234.13	NP_001157945.1	Q5T0N5-1B4DSI7
FNBP1L	NM_001024948.3 linkuse as main transcript	c.163C>G	p.Pro55Ala	missense_variant	3/14		NP_001020119.1	Q5T0N5-4
FNBP1L	NM_017737.5 linkuse as main transcript	c.163C>G	p.Pro55Ala	missense_variant	3/15		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.163C>G	p.Pro55Ala	missense_variant	3/17	5	NM_001164473.3	ENSP00000271234.7	Q5T0N5-1
FNBP1L	ENST00000260506.12 linkuse as main transcript	c.163C>G	p.Pro55Ala	missense_variant	3/14	1		ENSP00000260506.8	Q5T0N5-4
FNBP1L	ENST00000370253.6 linkuse as main transcript	c.163C>G	p.Pro55Ala	missense_variant	3/15	5		ENSP00000359275.2	Q5T0N5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.29e-7

AC:

AN:

1371238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

678750

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:

9.38e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Aug 22, 2023

The c.163C>G (p.P55A) alteration is located in exon 3 (coding exon 3) of the FNBP1L gene. This alteration results from a C to G substitution at nucleotide position 163, causing the proline (P) at amino acid position 55 to be replaced by an alanine (A). 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

0.30

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.50

D;D;D;D

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.9

L;L;.;L

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.0

D;D;.;D

REVEL

Benign

0.22

Sift

Uncertain

0.0010

D;D;.;D

Sift4G

Uncertain

0.025

D;D;D;D

Polyphen

1.0, 0.075

.;D;.;B

Vest4

0.57

MutPred

0.56

Loss of glycosylation at P55 (P = 0.0075);Loss of glycosylation at P55 (P = 0.0075);Loss of glycosylation at P55 (P = 0.0075);Loss of glycosylation at P55 (P = 0.0075);

MVP

0.43

MPC

0.94

ClinPred

1.0

GERP RS

5.5

Varity_R

0.57

gMVP

0.29

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

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