1-93529728-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001164473.3(FNBP1L):c.482C>T(p.Thr161Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000111 in 1,526,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

FNBP1L
NM_001164473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06510264).

BS2

High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FNBP1L	NM_001164473.3 linkuse as main transcript	c.482C>T	p.Thr161Ile	missense_variant	6/17	ENST00000271234.13
FNBP1L	NM_001024948.3 linkuse as main transcript	c.482C>T	p.Thr161Ile	missense_variant	6/14
FNBP1L	NM_017737.5 linkuse as main transcript	c.482C>T	p.Thr161Ile	missense_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNBP1L	ENST00000271234.13 linkuse as main transcript	c.482C>T	p.Thr161Ile	missense_variant	6/17	5	NM_001164473.3		Q5T0N5-1
FNBP1L	ENST00000260506.12 linkuse as main transcript	c.482C>T	p.Thr161Ile	missense_variant	6/14	1		P4	Q5T0N5-4
FNBP1L	ENST00000370253.6 linkuse as main transcript	c.482C>T	p.Thr161Ile	missense_variant	6/15	5		A1	Q5T0N5-3
FNBP1L	ENST00000424449.2 linkuse as main transcript	c.20C>T	p.Thr7Ile	missense_variant	1/12	2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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

GnomAD3 exomes

AF:

0.0000141

AC:

AN:

141928

Hom.:

AF XY:

0.0000133

AC XY:

AN XY:

75306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000609

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000265

GnomAD4 exome

AF:

0.00000582

AC:

AN:

1374792

Hom.:

Cov.:

AF XY:

0.00000295

AC XY:

AN XY:

678234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000699

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:

0.00000187

Gnomad4 OTH exome

AF:

0.0000698

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000524

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:

0.000200

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 22, 2023

The c.482C>T (p.T161I) alteration is located in exon 6 (coding exon 6) of the FNBP1L gene. This alteration results from a C to T substitution at nucleotide position 482, causing the threonine (T) at amino acid position 161 to be replaced by an isoleucine (I). 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

0.19

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Benign

0.14

DEOGEN2

Benign

0.022

T;.;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.075

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.0028

MetaRNN

Benign

0.065

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.2

N;N;.;N

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

2.1

N;N;.;N

REVEL

Benign

0.060

Sift

Benign

1.0

T;T;.;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0040, 0.0

.;B;.;B

Vest4

0.094

MutPred

0.35

Gain of MoRF binding (P = 0.1274);Gain of MoRF binding (P = 0.1274);Gain of MoRF binding (P = 0.1274);Gain of MoRF binding (P = 0.1274);

MVP

0.20

MPC

0.39

ClinPred

0.16

GERP RS

5.7

Varity_R

0.082

gMVP

0.093

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