rs758135384

Variant names:

• chr11-47724512-T-A
• rs758135384
• NM_015308.5:c.2275A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-47724512-T-A
• chr11-47724512-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015308.5(FNBP4):​c.2275A>T​(p.Thr759Ser) 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. 16/22 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. T759A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNBP4 NM_015308.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0730595).

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.2275A>T	p.Thr759Ser	missense	Exon 13 of 17	NP_056123.2	Q8N3X1-1
	FNBP4	NM_001441100.1		c.2500A>T	p.Thr834Ser	missense	Exon 14 of 18	NP_001428029.1
	FNBP4	NM_001441101.1		c.2500A>T	p.Thr834Ser	missense	Exon 14 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.2275A>T	p.Thr759Ser	missense	Exon 13 of 17	ENSP00000263773.5	Q8N3X1-1
	FNBP4	ENST00000917808.1		c.2494A>T	p.Thr832Ser	missense	Exon 14 of 18	ENSP00000587867.1
	FNBP4	ENST00000883715.1		c.2281A>T	p.Thr761Ser	missense	Exon 13 of 17	ENSP00000553774.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.058
Eigen_PC	Benign	0.054
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.79
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.075
Sift	Benign	0.18	T
Sift4G	Benign	0.84	T
Polyphen		0.33	B
Vest4		0.13
MutPred		0.072		Gain of glycosylation at T759 (P = 0.1326)
MVP		0.49
MPC		0.22
ClinPred		0.18	T
GERP RS		5.3
Varity_R		0.028
gMVP		0.053
Mutation Taster		=95/5	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: rs758135384; hg19: chr11-47746064;