17-45241901-C-T

Variant names:

• chr17-45241901-C-T
• rs1230236354
• NM_005892.4:c.1640C>T

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.1640C>T​(p.Pro547Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,266,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P547Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: FMNL1 NM_005892.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• 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=0.1591801).

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.1640C>T	p.Pro547Leu	missense	Exon 15 of 27	NP_005883.3
	FMNL1	NM_001411128.1		c.1640C>T	p.Pro547Leu	missense	Exon 15 of 26	NP_001398057.1	O95466-2
	FMNL1-AS1	NR_186807.1		n.-131G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL1	ENST00000331495.8	TSL:1 MANE Select	c.1640C>T	p.Pro547Leu	missense	Exon 15 of 27	ENSP00000329219.2	O95466-1
	FMNL1	ENST00000587489.6	TSL:1	c.1640C>T	p.Pro547Leu	missense	Exon 15 of 26	ENSP00000465474.2	K7EK60
	FMNL1	ENST00000947279.1		c.1658C>T	p.Pro553Leu	missense	Exon 17 of 28	ENSP00000617338.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1266788 Hom.: 0 Cov.: 35 AF XY: 0.00000322 AC XY: 2 AN XY: 620496

African (AFR) AF: 0.00 AC: 0 AN: 24638

American (AMR) AF: 0.00 AC: 0 AN: 17192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19042

East Asian (EAS) AF: 0.00 AC: 0 AN: 28854

South Asian (SAS) AF: 0.0000159 AC: 1 AN: 62950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3590

European-Non Finnish (NFE) AF: 9.73e-7 AC: 1 AN: 1027576

Other (OTH) AF: 0.00 AC: 0 AN: 52234

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.052
Sift	Benign	0.085	T
Sift4G	Uncertain	0.0030	D
Polyphen		0.19	B
Vest4		0.23
MutPred		0.34		Loss of glycosylation at P547 (P = 0.0061)
MVP		0.26
MPC		0.59
ClinPred		0.25	T
GERP RS		3.2
Varity_R		0.084
gMVP		0.14

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

dbSNP: rs1230236354; hg19: chr17-43319268;