chr11-47723281-C-T

Variant names:

• chr11-47723281-C-T
• rs1316365410
• NM_015308.5:c.2500G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015308.5(FNBP4):​c.2500G>A​(p.Gly834Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FNBP4 NM_015308.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63
• Publications: 1 publications found

Genes affected

FNBP4 (HGNC:19752): (formin binding protein 4) This gene encodes a protein containing two tryptophan-rich WW domains that binds the proline-rich formin homology 1 domains of formin family proteins, suggesting a role in the regulation of cytoskeletal dynamics during cell division and migration. It also binds intersectin family proteins suggesting a role in the maintenance of membrane curvature at sites of nascent vesicle formation. Naturally occurring mutations in this gene are associated with Waardenburg anophthalmia syndrome. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015308.5. 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
	FNBP4	NM_015308.5	MANE Select	c.2500G>A	p.Gly834Arg	missense	Exon 15 of 17	NP_056123.2	Q8N3X1-1
	FNBP4	NM_001441100.1		c.2725G>A	p.Gly909Arg	missense	Exon 16 of 18	NP_001428029.1
	FNBP4	NM_001441101.1		c.2725G>A	p.Gly909Arg	missense	Exon 16 of 18	NP_001428030.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP4	ENST00000263773.10	TSL:1 MANE Select	c.2500G>A	p.Gly834Arg	missense	Exon 15 of 17	ENSP00000263773.5	Q8N3X1-1
	FNBP4	ENST00000917808.1		c.2719G>A	p.Gly907Arg	missense	Exon 16 of 18	ENSP00000587867.1
	FNBP4	ENST00000883715.1		c.2506G>A	p.Gly836Arg	missense	Exon 15 of 17	ENSP00000553774.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000805 AC: 2 AN: 248474 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460078 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725998

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110596

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.058
Eigen_PC	Benign	-0.0080
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.15
Sift	Benign	0.13	T
Sift4G	Benign	0.24	T
Polyphen		0.43	B
Vest4		0.59
MutPred		0.49		Gain of MoRF binding (P = 0.011)
MVP		0.78
MPC		0.34
ClinPred		0.26	T
GERP RS		3.2
Varity_R		0.034
gMVP		0.57
Mutation Taster		=89/11	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: rs1316365410; hg19: chr11-47744833;