15-32776687-CTTTTTTTTTT-CTTTTTTTTTTTTTT

Variant names:

• chr15-32776687-C-CTTTT
• rs34593790
• NM_001277313.2:c.4215+144_4215+147dupAAAA

Variant summary

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

The NM_001277313.2(FMN1):​c.4215+144_4215+147dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 331,910 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: not found (cov: 29)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• 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 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+144_4215+147dupAAAA		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3546+144_3546+147dupAAAA		intron	N/A	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.4215+147_4215+148insAAAA		intron	N/A	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3546+147_3546+148insAAAA		intron	N/A	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3921+147_3921+148insAAAA		intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.0000121 AC: 4 AN: 331910 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 174670

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

African (AFR) AF: 0.00 AC: 0 AN: 9050

American (AMR) AF: 0.00 AC: 0 AN: 11082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10468

East Asian (EAS) AF: 0.00 AC: 0 AN: 23904

South Asian (SAS) AF: 0.00 AC: 0 AN: 27044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1984

European-Non Finnish (NFE) AF: 0.0000195 AC: 4 AN: 205326

Other (OTH) AF: 0.00 AC: 0 AN: 19520

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000316713), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs34593790; hg19: chr15-33068888;