chr1-240092508-C-T

Variant names:

• chr1-240092508-C-T
• rs375101837
• NM_020066.5:c.399C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_020066.5(FMN2):​c.399C>T​(p.Thr133Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000524 in 1,607,722 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (1 hom.)
• Consequence: FMN2 NM_020066.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.817

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-240092508-C-T is Benign according to our data. Variant chr1-240092508-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1336408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.817 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5	c.399C>T	p.Thr133Thr	synonymous_variant	Exon 1 of 18	ENST00000319653.14	NP_064450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14	c.399C>T	p.Thr133Thr	synonymous_variant	Exon 1 of 18	5	NM_020066.5	ENSP00000318884.9
FMN2	ENST00000447095.5	c.-87+24435C>T		intron_variant	Intron 2 of 6	3		ENSP00000409308.1

Frequencies

GnomAD3 genomes AF: 0.000428 AC: 65 AN: 151990 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000309 AC: 72 AN: 232890 AF XY: 0.000330

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000303

Gnomad ASJ exome AF: 0.000624

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000494

Gnomad NFE exome AF: 0.000599

Gnomad OTH exome AF: 0.000350

GnomAD4 exome AF: 0.000534 AC: 778 AN: 1455732 Hom.: 1 Cov.: 89 AF XY: 0.000533 AC XY: 386 AN XY: 723812

Gnomad4 AFR exome AF: 0.000180 AC: 6 AN: 33358

Gnomad4 AMR exome AF: 0.0000458 AC: 2 AN: 43692

Gnomad4 ASJ exome AF: 0.000617 AC: 16 AN: 25936

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39466

Gnomad4 SAS exome AF: 0.0000117 AC: 1 AN: 85600

Gnomad4 FIN exome AF: 0.000133 AC: 7 AN: 52442

Gnomad4 NFE exome AF: 0.000649 AC: 720 AN: 1109360

Gnomad4 Remaining exome AF: 0.000433 AC: 26 AN: 60112

GnomAD4 genome AF: 0.000428 AC: 65 AN: 151990 Hom.: 0 Cov.: 33 AF XY: 0.000350 AC XY: 26 AN XY: 74216

Gnomad4 AFR AF: 0.0000241 AC: 0.0000241499 AN: 0.0000241499

Gnomad4 AMR AF: 0.000131 AC: 0.000130959 AN: 0.000130959

Gnomad4 ASJ AF: 0.000577 AC: 0.000576701 AN: 0.000576701

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.000188 AC: 0.000188466 AN: 0.000188466

Gnomad4 NFE AF: 0.000853 AC: 0.000853016 AN: 0.000853016

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000808 Hom.: 0

Bravo AF: 0.000351

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Apr 25, 2018

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FMN2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.7
DANN	Benign	0.91
Mutation Taster		=100/0	polymorphism

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: rs375101837; hg19: chr1-240255808;