1-240093139-G-T

Position:

• chr1-240093139-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020066.5(FMN2):​c.1030G>T​(p.Asp344Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FMN2 NM_020066.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41531268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN2	NM_020066.5	c.1030G>T	p.Asp344Tyr	missense_variant	1/18	ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.1030G>T	p.Asp344Tyr	missense_variant	1/18	5	NM_020066.5	ENSP00000318884	P1
FMN2	ENST00000447095.5	c.-87+25066G>T		intron_variant		3		ENSP00000409308

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000308 AC: 1 AN: 32432 Hom.: 0 AF XY: 0.0000612 AC XY: 1 AN XY: 16342

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000181

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1262048 Hom.: 0 Cov.: 86 AF XY: 0.00 AC XY: 0 AN XY: 612146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.94	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.051	T
Polyphen		1.0	D
Vest4		0.42
MutPred		0.13		Gain of phosphorylation at D344 (P = 0.009);
MVP		0.43
MPC		0.97
ClinPred		0.46	T
GERP RS		3.7
Varity_R		0.39
gMVP		0.25

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: rs559793960; hg19: chr1-240256439;