NM_020066.5:c.4910+173T>C

Variant names:

• chr1-240392735-T-C
• rs9730073
• NM_020066.5:c.4910+173T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020066.5(FMN2):​c.4910+173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,030 control chromosomes in the GnomAD database, including 24,282 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (24282 hom., cov: 33)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 2 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	NM_020066.5	MANE Select	c.4910+173T>C		intron	N/A	NP_064450.3
	FMN2	NM_001305424.2		c.4922+173T>C		intron	N/A	NP_001292353.1
	FMN2	NM_001348094.2		c.2738+173T>C		intron	N/A	NP_001335023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	ENST00000319653.14	TSL:5 MANE Select	c.4910+173T>C		intron	N/A	ENSP00000318884.9
	FMN2	ENST00000679980.1		c.1178+173T>C		intron	N/A	ENSP00000505449.1
	FMN2	ENST00000681210.1		c.1130+173T>C		intron	N/A	ENSP00000505131.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83132 AN: 151910 Hom.: 24225 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.527

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.548 AC: 83253 AN: 152030 Hom.: 24282 Cov.: 33 AF XY: 0.542 AC XY: 40272 AN XY: 74330

African (AFR) AF: 0.752 AC: 31202 AN: 41480

American (AMR) AF: 0.560 AC: 8552 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3466

East Asian (EAS) AF: 0.659 AC: 3400 AN: 5160

South Asian (SAS) AF: 0.491 AC: 2367 AN: 4820

European-Finnish (FIN) AF: 0.358 AC: 3785 AN: 10570

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.451 AC: 30624 AN: 67948

Other (OTH) AF: 0.535 AC: 1128 AN: 2108

Alfa AF: 0.495 Hom.: 2358

Bravo AF: 0.574

Asia WGS AF: 0.611 AC: 2118 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.19
DANN	Benign	0.60
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs9730073; hg19: chr1-240556035;