Genetic Variant FMN1:p.Phe1352Phe (chr15-32798878-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001277313.2(FMN1):c.4056T>C(p.Phe1352Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,612,918 control chromosomes in the GnomAD database, including 16,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1840 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15096 hom. )

Consequence

FMN1
NM_001277313.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.79

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:

LOC107984089 (HGNC:):

LOC107984089 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 15-32798878-A-G is Benign according to our data. Variant chr15-32798878-A-G is described in ClinVar as [Benign]. Clinvar id is 1264971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN1	NM_001277313.2 link	c.4056T>C	p.Phe1352Phe	synonymous_variant	Exon 19 of 21	ENST00000616417.5	NP_001264242.1	Q68DA7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5 link	c.4056T>C	p.Phe1352Phe	synonymous_variant	Exon 19 of 21	5	NM_001277313.2	ENSP00000479134.1		Q68DA7-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23365

AN:

151886

Hom.:

1839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.140

AC:

34743

AN:

248240

Hom.:

2512

AF XY:

0.143

AC XY:

19196

AN XY:

134652

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.142

AC:

207793

AN:

1460916

Hom.:

15096

Cov.:

AF XY:

0.143

AC XY:

103975

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.167

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.173

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.154

AC:

23374

AN:

152002

Hom.:

1840

Cov.:

AF XY:

0.152

AC XY:

11320

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.175

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.147

Hom.:

3231

Bravo

AF:

0.155

Asia WGS

AF:

0.167

AC:

580

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.6

DANN

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over