SCYL3 p.Phe662Leu

Variant names:

• chr1-169854291-A-T
• NM_020423.7:c.1986T>A
• SCYL3 p.Phe662Leu

Your query was ambiguous. Multiple possible variants found:

• chr1-169854291-A-T
• chr1-169854291-A-C
• chr1-169854293-A-G
• chr1-169854291-AAA-GAG
• chr1-169854291-AAA-TAG
• chr1-169854291-AAA-CAG

Variant summary

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

The NM_020423.7(SCYL3):​c.1986T>A​(p.Phe662Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: SCYL3 NM_020423.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 0 publications found

Genes affected

SCYL3 (HGNC:19285): (SCY1 like pseudokinase 3) This gene encodes a protein with a kinase domain and four HEAT repeats. The encoded protein interacts with the C-terminal domain of ezrin, an ERM protein, and may play a role in cell adhesion and migration. Alternative splicing results in multiple transcript variants encoding multiple isoforms. [provided by RefSeq, Jun 2012]

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020423.7. 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
	SCYL3	NM_020423.7	MANE Select	c.1986T>A	p.Phe662Leu	missense	Exon 12 of 13	NP_065156.5
	SCYL3	NM_181093.4		c.2148T>A	p.Phe716Leu	missense	Exon 13 of 14	NP_851607.2	Q8IZE3-1
	FIRRM	NM_001320047.2	MANE Select	c.*1304A>T		downstream_gene	N/A	NP_001306976.1	Q9NSG2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCYL3	ENST00000367771.11	TSL:1 MANE Select	c.1986T>A	p.Phe662Leu	missense	Exon 12 of 13	ENSP00000356745.5	Q8IZE3-2
	SCYL3	ENST00000367770.5	TSL:1	c.2148T>A	p.Phe716Leu	missense	Exon 12 of 13	ENSP00000356744.1	Q8IZE3-1
	SCYL3	ENST00000910084.1		c.2187T>A	p.Phe729Leu	missense	Exon 14 of 15	ENSP00000580143.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.60
gMVP		0.29
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-169823432;