9-129902922-C-T

Variant names:

• chr9-129902922-C-T
• NM_015033.3:c.1375G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015033.3(FNBP1):​c.1375G>A​(p.Ala459Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNBP1 NM_015033.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.217

Genes affected

FNBP1 (HGNC:17069): (formin binding protein 1) The protein encoded by this gene is a member of the formin-binding-protein family. The protein contains an N-terminal Fer/Cdc42-interacting protein 4 (CIP4) homology (FCH) domain followed by a coiled-coil domain, a proline-rich motif, a second coiled-coil domain, a Rho family protein-binding domain (RBD), and a C-terminal SH3 domain. This protein binds sorting nexin 2 (SNX2), tankyrase (TNKS), and dynamin; an interaction between this protein and formin has not been demonstrated yet in human. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03559646).
• BP6: Variant 9-129902922-C-T is Benign according to our data. Variant chr9-129902922-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2337795.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP1	NM_015033.3	c.1375G>A	p.Ala459Thr	missense_variant	Exon 13 of 17	ENST00000446176.7	NP_055848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNBP1	ENST00000446176.7	c.1375G>A	p.Ala459Thr	missense_variant	Exon 13 of 17	1	NM_015033.3	ENSP00000413625.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 20, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.4
DANN	Benign	0.68
DEOGEN2	Benign	0.078	T;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.036	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.45	N;.;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.68	N;.;.;N
REVEL	Benign	0.12
Sift	Benign	0.67	T;.;.;T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.11
MutPred		0.19		Gain of phosphorylation at A459 (P = 0.0647);.;.;.;
MVP		0.58
MPC		0.19
ClinPred		0.031	T
GERP RS		-6.8
Varity_R		0.026
gMVP		0.055

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-132665201;