SCYL3 p.Lys594Lys

Variant names:

• chr1-169854494-C-C
• ENST00000359326.9:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-169854495--
• chr1-169854495-C-T

Variant summary

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

The NM_020423.7(SCYL3):​c. variant causes a exon region 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCYL3 NM_020423.7 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988
• Publications: 0 publications found

Genes affected

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

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]

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.		exon_region	Exon 12 of 13	NP_065156.5
	SCYL3	NM_181093.4		c.		exon_region	Exon 13 of 14	NP_851607.2	Q8IZE3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIRRM	ENST00000359326.9	TSL:1 MANE Select	c.		exon_region	Exon 25 of 25	ENSP00000352276.4	Q9NSG2-1
	SCYL3	ENST00000367771.11	TSL:1 MANE Select	c.		exon_region	Exon 12 of 13	ENSP00000356745.5	Q8IZE3-2
	FIRRM	ENST00000286031.10	TSL:1	c.		exon_region	Exon 24 of 24	ENSP00000286031.6	Q9NSG2-1

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
PhyloP100		-0.99

Splicing

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: chr1-169823635;