NM_001277313.2:c.2057T>C

Variant names:

• chr15-33065061-A-G
• rs2306277
• NM_001277313.2:c.2057T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277313.2(FMN1):​c.2057T>C​(p.Leu686Pro) variant causes a missense change. The variant allele was found at a frequency of 0.546 in 1,606,420 control chromosomes in the GnomAD database, including 243,334 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20840 hom., cov: 32)
  • Exomes 𝑓: 0.55 (222494 hom.)
• Consequence: FMN1 NM_001277313.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.67
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.9634964E-5).
• BP6: Variant 15-33065061-A-G is Benign according to our data. Variant chr15-33065061-A-G is described in ClinVar as Benign. ClinVar VariationId is 1265497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.2057T>C	p.Leu686Pro	missense_variant	Exon 6 of 21	ENST00000616417.5	NP_001264242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.2057T>C	p.Leu686Pro	missense_variant	Exon 6 of 21	5	NM_001277313.2	ENSP00000479134.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78654 AN: 151910 Hom.: 20833 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.539

GnomAD2 exomes AF: 0.528 AC: 129243 AN: 244892 AF XY: 0.532

Gnomad AFR exome AF: 0.449

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.670

Gnomad EAS exome AF: 0.218

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.556

GnomAD4 exome AF: 0.549 AC: 798225 AN: 1454392 Hom.: 222494 Cov.: 32 AF XY: 0.549 AC XY: 397064 AN XY: 723428

African (AFR) AF: 0.453 AC: 15042 AN: 33234

American (AMR) AF: 0.534 AC: 23492 AN: 44026

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 17312 AN: 26060

East Asian (EAS) AF: 0.232 AC: 9148 AN: 39466

South Asian (SAS) AF: 0.544 AC: 46267 AN: 84986

European-Finnish (FIN) AF: 0.541 AC: 28845 AN: 53302

Middle Eastern (MID) AF: 0.582 AC: 3348 AN: 5750

European-Non Finnish (NFE) AF: 0.561 AC: 621759 AN: 1107480

Other (OTH) AF: 0.549 AC: 33012 AN: 60088

GnomAD4 genome AF: 0.518 AC: 78694 AN: 152028 Hom.: 20840 Cov.: 32 AF XY: 0.516 AC XY: 38371 AN XY: 74326

African (AFR) AF: 0.455 AC: 18864 AN: 41420

American (AMR) AF: 0.543 AC: 8289 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2340 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1120 AN: 5170

South Asian (SAS) AF: 0.537 AC: 2587 AN: 4816

European-Finnish (FIN) AF: 0.535 AC: 5651 AN: 10568

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37922 AN: 67992

Other (OTH) AF: 0.541 AC: 1139 AN: 2106

Alfa AF: 0.546 Hom.: 69286

Bravo AF: 0.516

TwinsUK AF: 0.564 AC: 2093

ALSPAC AF: 0.539 AC: 2076

ESP6500AA AF: 0.461 AC: 1766

ESP6500EA AF: 0.572 AC: 4721

ExAC AF: 0.530 AC: 64013

Asia WGS AF: 0.406 AC: 1415 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.034
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.76
DEOGEN2	Benign	0.050	T;.;T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.0	.;.;.;.
MetaRNN	Benign	0.000030	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.7	N;.;N;.
PhyloP100		6.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.0	.;N;N;N
REVEL	Benign	0.0
Sift	Pathogenic	0.0	.;T;T;T
Sift4G	Benign	0.24	T;T;T;T
Vest4		0.082
ClinPred		0.0050	T
GERP RS		5.1
Varity_R		0.21
gMVP		0.12
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: rs2306277; hg19: chr15-33357262; COSMIC: COSV57916979;