NM_005892.4:c.908A>C

Variant names:

• chr17-45238577-A-C
• NM_005892.4:c.908A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005892.4(FMNL1):​c.908A>C​(p.Gln303Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FMNL1 NM_005892.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.0635496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL1	NM_005892.4	c.908A>C	p.Gln303Pro	missense_variant	Exon 10 of 27	ENST00000331495.8	NP_005883.3
FMNL1	NM_001411128.1	c.908A>C	p.Gln303Pro	missense_variant	Exon 10 of 26		NP_001398057.1
FMNL1-AS1	NR_186807.1	n.1490T>G		non_coding_transcript_exon_variant	Exon 2 of 2
FMNL1-AS1	NR_186808.1	n.1440T>G		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMNL1	ENST00000331495.8	c.908A>C	p.Gln303Pro	missense_variant	Exon 10 of 27	1	NM_005892.4	ENSP00000329219.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727232

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.908A>C (p.Q303P) alteration is located in exon 10 (coding exon 10) of the FMNL1 gene. This alteration results from a A to C substitution at nucleotide position 908, causing the glutamine (Q) at amino acid position 303 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Benign	0.96
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.033	D
ClinPred		0.39	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr17-43315944;