15-32774363-GAA-GAAAA

Variant names:

• chr15-32774363-G-GAA
• rs747880801
• NM_001277313.2:c.4216-11_4216-10dupTT

Variant summary

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

The NM_001277313.2(FMN1):​c.4216-11_4216-10dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000362 in 1,382,034 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: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: FMN1 NM_001277313.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• 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.4216-11_4216-10dupTT		intron	N/A	NP_001264242.1	Q68DA7-1
	FMN1	NM_001103184.4		c.3547-11_3547-10dupTT		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.4216-10_4216-9insTT		intron	N/A	ENSP00000479134.1	Q68DA7-1
	FMN1	ENST00000334528.13	TSL:1	c.3547-10_3547-9insTT		intron	N/A	ENSP00000333950.9	Q68DA7-5
	FMN1	ENST00000561249.5	TSL:5	c.3922-10_3922-9insTT		intron	N/A	ENSP00000453443.1	H0YM30

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000362 AC: 5 AN: 1382034 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 685600

⚠️ 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: 30804

American (AMR) AF: 0.0000292 AC: 1 AN: 34216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24424

East Asian (EAS) AF: 0.00 AC: 0 AN: 38324

South Asian (SAS) AF: 0.00 AC: 0 AN: 77498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 0.00000376 AC: 4 AN: 1062938

Other (OTH) AF: 0.00 AC: 0 AN: 57242

⚠️ 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.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24

Splicing

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

Other links and lift over

dbSNP: rs747880801; hg19: chr15-33066564;