15-32774363-G-GA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001277313.2(FMN1):c.4216-10_4216-9insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000853 in 1,522,226 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (0 hom.)
• Consequence: FMN1 NM_001277313.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.240

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-32774363-G-GA is Benign according to our data. Variant chr15-32774363-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 2756056.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN1	NM_001277313.2	c.4216-10_4216-9insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000616417.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN1	ENST00000616417.5	c.4216-10_4216-9insT		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001277313.2	A2

Frequencies

GnomAD3 genomes AF: 0.000241 AC: 36 AN: 149582 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000713

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000594

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000920 AC: 1263 AN: 1372644 Hom.: 0 Cov.: 27 AF XY: 0.000863 AC XY: 588 AN XY: 681038

Gnomad4 AFR exome AF: 0.00170

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.000453

Gnomad4 EAS exome AF: 0.000367

Gnomad4 SAS exome AF: 0.000830

Gnomad4 FIN exome AF: 0.000177

Gnomad4 NFE exome AF: 0.000940

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.000241 AC: 36 AN: 149582 Hom.: 0 Cov.: 32 AF XY: 0.000247 AC XY: 18 AN XY: 72896

Gnomad4 AFR AF: 0.000713

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000594

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000242

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 12, 2023

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs747880801; hg19: chr15-33066564;