chr1-240092109-C-T

Variant names:

• chr1-240092109-C-T
• rs1660992161
• NM_020066.5:c.-1C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020066.5(FMN2):​c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FMN2 NM_020066.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60
• Publications: 0 publications found

Genes affected

FMN2 (HGNC:14074): (formin 2) This gene is a member of the formin homology protein family. The encoded protein is thought to have essential roles in organization of the actin cytoskeleton and in cell polarity. This protein mediates the formation of an actin mesh that positions the spindle during oogenesis and also regulates the formation of actin filaments in the nucleus. This protein also forms a perinuclear actin/focal-adhesion system that regulates the shape and position of the nucleus during cell migration. Mutations in this gene have been associated with infertility and also with an autosomal recessive form of intellectual disability (MRT47). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2017]

FMN2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 47

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020066.5. 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
	FMN2	NM_020066.5	MANE Select	c.-1C>T		5_prime_UTR	Exon 1 of 18	NP_064450.3
	FMN2	NM_001305424.2		c.-1C>T		5_prime_UTR	Exon 1 of 19	NP_001292353.1
	FMN2	NM_001348094.2		c.-1C>T		5_prime_UTR	Exon 1 of 15	NP_001335023.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	ENST00000319653.14	TSL:5 MANE Select	c.-1C>T		5_prime_UTR	Exon 1 of 18	ENSP00000318884.9	Q9NZ56-1
	FMN2	ENST00000447095.5	TSL:3	c.-87+24036C>T		intron	N/A	ENSP00000409308.1	B0QZA8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396864 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 688964

African (AFR) AF: 0.00 AC: 0 AN: 31884

American (AMR) AF: 0.00 AC: 0 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24992

East Asian (EAS) AF: 0.00 AC: 0 AN: 36198

South Asian (SAS) AF: 0.00 AC: 0 AN: 79016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079710

Other (OTH) AF: 0.0000173 AC: 1 AN: 57946

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.97
PhyloP100		1.6
PromoterAI		-0.056	Neutral

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

Other links and lift over

dbSNP: rs1660992161; hg19: chr1-240255409;