NM_001277313.2:c.4246G>A

Variant names:

• chr15-32774324-C-T
• rs2056344395
• NM_001277313.2:c.4246G>A

Variant summary

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

The NM_001277313.2(FMN1):​c.4246G>A​(p.Val1416Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FMN1 NM_001277313.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32
• Publications: 0 publications found

Genes affected

FMN1 (HGNC:3768): (formin 1) This gene belongs to the formin homology family and encodes a protein that has a role in the formation of adherens junction and the polymerization of linear actin cables. The homologous gene in mouse is associated with limb deformity. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

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=0.19747502).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277313.2. 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
	FMN1	NM_001277313.2	MANE Select	c.4246G>A	p.Val1416Met	missense	Exon 21 of 21	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3577G>A	p.Val1193Met	missense	Exon 17 of 17	NP_001096654.1	Q68DA7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN1	ENST00000616417.5	TSL:5 MANE Select	c.4246G>A	p.Val1416Met	missense	Exon 21 of 21	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3577G>A	p.Val1193Met	missense	Exon 17 of 17	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3952G>A	p.Val1318Met	missense	Exon 16 of 16	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.19
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.66	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.77	P
Vest4		0.23
MutPred		0.13		Loss of phosphorylation at T1195 (P = 0.1136)
MVP		0.60
MPC		0.053
ClinPred		0.87	D
GERP RS		5.2
Varity_R		0.18
gMVP		0.28
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2056344395; hg19: chr15-33066525;