Genetic Variant NM_001164473.3:c.230A>G (chr1-93523379-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001164473.3(FNBP1L):c.230A>G(p.Asn77Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,114 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: 6.9e-7 ( 0 hom. )

Consequence

FNBP1L
NM_001164473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.71

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP1L	NM_001164473.3 link	c.230A>G	p.Asn77Ser	missense_variant	Exon 4 of 17	ENST00000271234.13	NP_001157945.1	Q5T0N5-1B4DSI7
FNBP1L	NM_001024948.3 link	c.230A>G	p.Asn77Ser	missense_variant	Exon 4 of 14		NP_001020119.1	Q5T0N5-4
FNBP1L	NM_017737.5 link	c.230A>G	p.Asn77Ser	missense_variant	Exon 4 of 15		NP_060207.2	Q5T0N5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FNBP1L	ENST00000271234.13 link	c.230A>G	p.Asn77Ser	missense_variant	Exon 4 of 17	5	NM_001164473.3	ENSP00000271234.7	Q5T0N5-1
FNBP1L	ENST00000260506.12 link	c.230A>G	p.Asn77Ser	missense_variant	Exon 4 of 14	1		ENSP00000260506.8	Q5T0N5-4
FNBP1L	ENST00000370253.6 link	c.230A>G	p.Asn77Ser	missense_variant	Exon 4 of 15	5		ENSP00000359275.2	Q5T0N5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000418

AC:

AN:

239284

Hom.:

AF XY:

0.00000773

AC XY:

AN XY:

129336

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:

0.0000345

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456114

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723644

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 10, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230A>G (p.N77S) alteration is located in exon 4 (coding exon 4) of the FNBP1L gene. This alteration results from a A to G substitution at nucleotide position 230, causing the asparagine (N) at amino acid position 77 to be replaced by a serine (S). 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

0.072

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.;.;.

Eigen

Benign

0.026

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.43

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.;L

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.4

N;N;.;N

REVEL

Benign

0.14

Sift

Benign

0.046

D;D;.;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.0020, 0.0

.;B;.;B

Vest4

0.55

MutPred

0.47

Gain of phosphorylation at Y82 (P = 0.1815);Gain of phosphorylation at Y82 (P = 0.1815);Gain of phosphorylation at Y82 (P = 0.1815);Gain of phosphorylation at Y82 (P = 0.1815);

MVP

0.57

MPC

0.29

ClinPred

0.32

GERP RS

6.0

Varity_R

0.21

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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