9-129895973-C-G

Variant names:

• chr9-129895973-C-G
• rs747213580
• NM_015033.3:c.1711G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015033.3(FNBP1):​c.1711G>C​(p.Val571Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,457,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V571A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: FNBP1 NM_015033.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19720572).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015033.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP1	NM_015033.3	MANE Select	c.1711G>C	p.Val571Leu	missense	Exon 16 of 17	NP_055848.1	Q96RU3-1
	FNBP1	NM_001438006.1		c.1795G>C	p.Val599Leu	missense	Exon 17 of 18	NP_001424935.1	A0A8V8TQ35
	FNBP1	NM_001439039.1		c.1780G>C	p.Val594Leu	missense	Exon 16 of 16	NP_001425968.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP1	ENST00000446176.7	TSL:1 MANE Select	c.1711G>C	p.Val571Leu	missense	Exon 16 of 17	ENSP00000413625.1	Q96RU3-1
	FNBP1	ENST00000699492.1		c.1795G>C	p.Val599Leu	missense	Exon 17 of 18	ENSP00000514403.1	A0A8V8TQ35
	FNBP1	ENST00000703559.1		c.1714G>C	p.Val572Leu	missense	Exon 16 of 16	ENSP00000515375.1	A0A994J3V8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000246 AC: 6 AN: 244122 AF XY: 0.0000226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000181

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1457298 Hom.: 0 Cov.: 33 AF XY: 0.00000414 AC XY: 3 AN XY: 724800

African (AFR) AF: 0.00 AC: 0 AN: 33172

American (AMR) AF: 0.000183 AC: 8 AN: 43668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 85046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110526

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.10
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.020	D
Polyphen		0.057	B
Vest4		0.49
MutPred		0.44		Loss of glycosylation at T568 (P = 0.1941)
MVP		0.54
MPC		0.23
ClinPred		0.15	T
GERP RS		4.2
Varity_R		0.10
gMVP		0.44
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs747213580; hg19: chr9-132658252;