Variant 1-93536368-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164473.3(FNBP1L):c.1027A>C(p.Thr343Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,548,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

FNBP1L
NM_001164473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

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=0.06686884).

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNBP1L	NM_001164473.3 linkuse as main transcript	c.1027A>C	p.Thr343Pro	missense_variant	10/17	ENST00000271234.13	NP_001157945.1	Q5T0N5-1B4DSI7
FNBP1L	NM_001024948.3 linkuse as main transcript	c.990+1460A>C		intron_variant			NP_001020119.1	Q5T0N5-4
FNBP1L	NM_017737.5 linkuse as main transcript	c.990+1460A>C		intron_variant			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.1027A>C	p.Thr343Pro	missense_variant	10/17	5	NM_001164473.3	ENSP00000271234.7	Q5T0N5-1
FNBP1L	ENST00000260506.12 linkuse as main transcript	c.990+1460A>C		intron_variant		1		ENSP00000260506.8	Q5T0N5-4
FNBP1L	ENST00000424449.2 linkuse as main transcript	c.562A>C	p.Thr188Pro	missense_variant	5/12	2		ENSP00000397451.2	A0A075B6Q2
FNBP1L	ENST00000370253.6 linkuse as main transcript	c.990+1460A>C		intron_variant		5		ENSP00000359275.2	Q5T0N5-3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151990

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000192

AC:

AN:

156576

Hom.:

AF XY:

0.0000121

AC XY:

AN XY:

82736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000492

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1396770

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

688992

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

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:

0.0000176

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74252

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000778

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000394

AC:

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

Oct 25, 2023

The c.1027A>C (p.T343P) alteration is located in exon 10 (coding exon 10) of the FNBP1L gene. This alteration results from a A to C substitution at nucleotide position 1027, causing the threonine (T) at amino acid position 343 to be replaced by a proline (P). 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

0.049

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.32

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.6

N;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.8

N;.

REVEL

Benign

0.18

Sift

Benign

1.0

T;.

Sift4G

Benign

0.57

T;T

Vest4

0.20

MutPred

0.15

Gain of glycosylation at T346 (P = 0.1227);Gain of glycosylation at T346 (P = 0.1227);

MVP

0.48

MPC

0.47

ClinPred

0.060

GERP RS

5.2

Varity_R

0.20

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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