NM_001277313.2:c.4064G>C

Variant names:

• chr15-32798870-C-G
• rs896217892
• NM_001277313.2:c.4064G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001277313.2(FMN1):​c.4064G>C​(p.Trp1355Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.54

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]

LOC107984089 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.4064G>C	p.Trp1355Ser	missense_variant	Exon 19 of 21	ENST00000616417.5	NP_001264242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.4064G>C	p.Trp1355Ser	missense_variant	Exon 19 of 21	5	NM_001277313.2	ENSP00000479134.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3395G>C (p.W1132S) alteration is located in exon 15 (coding exon 15) of the FMN1 gene. This alteration results from a G to C substitution at nucleotide position 3395, causing the tryptophan (W) at amino acid position 1132 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;T;T
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Pathogenic	3.0	M;.;.;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-11	.;D;D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.021	.;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.89
MutPred		0.73		.;Gain of disorder (P = 0.0426);.;.;
MVP		0.63
MPC		0.21
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.89
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs896217892; hg19: chr15-33091071;