NM_005892.4:c.1343G>A

Variant names:

• chr17-45241392-G-A
• NM_005892.4:c.1343G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005892.4(FMNL1):​c.1343G>A​(p.Ser448Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,416,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FMNL1 NM_005892.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.353
• Publications: 0 publications found

Genes affected

FMNL1 (HGNC:1212): (formin like 1) This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. An alternative splice variant has been described but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]

FMNL1-AS1 (HGNC:55717): (FMNL1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07033822).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005892.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL1	NM_005892.4	MANE Select	c.1343G>A	p.Ser448Asn	missense	Exon 14 of 27	NP_005883.3
	FMNL1	NM_001411128.1		c.1343G>A	p.Ser448Asn	missense	Exon 14 of 26	NP_001398057.1	O95466-2
	FMNL1-AS1	NR_186807.1		n.379C>T		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL1	ENST00000331495.8	TSL:1 MANE Select	c.1343G>A	p.Ser448Asn	missense	Exon 14 of 27	ENSP00000329219.2	O95466-1
	FMNL1	ENST00000587489.6	TSL:1	c.1343G>A	p.Ser448Asn	missense	Exon 14 of 26	ENSP00000465474.2	K7EK60
	FMNL1	ENST00000947279.1		c.1361G>A	p.Ser454Asn	missense	Exon 16 of 28	ENSP00000617338.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1416896 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 701474

African (AFR) AF: 0.00 AC: 0 AN: 32192

American (AMR) AF: 0.00 AC: 0 AN: 37866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25184

East Asian (EAS) AF: 0.00 AC: 0 AN: 37122

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5508

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089768

Other (OTH) AF: 0.00 AC: 0 AN: 58568

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.35
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.062
Sift	Benign	0.067	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.19		Loss of phosphorylation at S448 (P = 0.003)
MVP		0.35
MPC		0.54
ClinPred		0.061	T
GERP RS		1.5
PromoterAI		-0.0066	Neutral
Varity_R		0.073
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr17-43318759;