dbSNP rs2140870327: FMN1:p.Leu1378Val (chr15-32776918-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001277313.2(FMN1):c.4132T>G(p.Leu1378Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,419,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1378L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

FMN1
NM_001277313.2 missense, splice_region

Scores

Splicing: ADA: 0.0002593

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.725

Publications

0 publications found

Variant links:

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]

FMN1 links:

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ACMG classification

Classification was made for transcript

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=0.16130632).

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.4132T>G	p.Leu1378Val	missense splice_region	Exon 20 of 21	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3463T>G	p.Leu1155Val	missense splice_region	Exon 16 of 17	NP_001096654.1	Q68DA7-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FMN1	ENST00000616417.5	TSL:5 MANE Select	c.4132T>G	p.Leu1378Val	missense splice_region	Exon 20 of 21	ENSP00000479134.1	Q68DA7-1
FMN1	ENST00000334528.13	TSL:1	c.3463T>G	p.Leu1155Val	missense splice_region	Exon 16 of 17	ENSP00000333950.9	Q68DA7-5
FMN1	ENST00000561249.5	TSL:5	c.3838T>G	p.Leu1280Val	missense splice_region	Exon 15 of 16	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1419346

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32786

American (AMR)

AF:

0.00

AC:

AN:

40708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25506

East Asian (EAS)

AF:

0.00

AC:

AN:

39094

South Asian (SAS)

AF:

0.00

AC:

AN:

81678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

9.23e-7

AC:

AN:

1082928

Other (OTH)

AF:

0.00

AC:

AN:

59002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.58

M_CAP

Benign

0.027

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.9

PhyloP100

0.72

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.70

REVEL

Benign

0.16

Sift

Benign

0.15

Sift4G

Benign

0.48

Polyphen

0.87

Vest4

0.20

MutPred

0.31

Loss of catalytic residue at L1155 (P = 0.0101)

MVP

0.54

MPC

0.17

ClinPred

0.82

GERP RS

-3.2

Varity_R

0.15

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00026

dbscSNV1_RF

Benign

0.022

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over