Genetic Variant FMN1:c.4215+145_4215+147dupAAA (chr15-32776687-C-CTTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001277313.2(FMN1):c.4215+145_4215+147dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000964 in 331,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000096 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FMN1
NM_001277313.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.533

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.4215+145_4215+147dupAAA		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3546+145_3546+147dupAAA		intron	N/A	NP_001096654.1	Q68DA7-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FMN1	ENST00000616417.5	TSL:5 MANE Select	c.4215+147_4215+148insAAA	intron	N/A	ENSP00000479134.1	Q68DA7-1
FMN1	ENST00000334528.13	TSL:1	c.3546+147_3546+148insAAA	intron	N/A	ENSP00000333950.9	Q68DA7-5
FMN1	ENST00000561249.5	TSL:5	c.3921+147_3921+148insAAA	intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

122390

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000964

AC:

AN:

331862

Hom.:

AF XY:

0.0000916

AC XY:

AN XY:

174654

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000221

AC:

AN:

9050

American (AMR)

AF:

0.0000903

AC:

AN:

11080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10464

East Asian (EAS)

AF:

0.00

AC:

AN:

23908

South Asian (SAS)

AF:

0.000222

AC:

AN:

27040

European-Finnish (FIN)

AF:

0.000128

AC:

AN:

23528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1984

European-Non Finnish (NFE)

AF:

0.0000974

AC:

AN:

205296

Other (OTH)

AF:

0.00

AC:

AN:

19512

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.261

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

122390

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

58872

African (AFR)

AF:

0.00

AC:

AN:

31460

American (AMR)

AF:

0.00

AC:

AN:

12314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2920

East Asian (EAS)

AF:

0.00

AC:

AN:

4408

South Asian (SAS)

AF:

0.00

AC:

AN:

3844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57792

Other (OTH)

AF:

0.00

AC:

AN:

1590

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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15-32776687-CTTTTTTTTTT-CTTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over