15-32776874-C-G

Variant names:

• chr15-32776874-C-G
• NM_001277313.2:c.4176G>C

Variant summary

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

The NM_001277313.2(FMN1):​c.4176G>C​(p.Lys1392Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FMN1 NM_001277313.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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

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=0.29622233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.4176G>C	p.Lys1392Asn	missense_variant	Exon 20 of 21	ENST00000616417.5	NP_001264242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.4176G>C	p.Lys1392Asn	missense_variant	Exon 20 of 21	5	NM_001277313.2	ENSP00000479134.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445448 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 717248

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: 0.0000167

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.6	L;.;.;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.7	.;D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.016	.;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.34
MutPred		0.33		.;Loss of methylation at K1169 (P = 0.0116);.;.;
MVP		0.68
MPC		0.20
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.67
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-33069075;