rs1386750013

Variant names:

• chr1-169854554-C-A
• rs1386750013
• NM_020423.7:c.1723G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-169854554-C-A
• chr1-169854554-C-T

Variant summary

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

The NM_020423.7(SCYL3):​c.1723G>T​(p.Gly575Trp) 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 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. G575R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCYL3 NM_020423.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09248316).

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.1723G>T	p.Gly575Trp	missense	Exon 12 of 13	NP_065156.5
	SCYL3	NM_181093.4		c.1885G>T	p.Gly629Trp	missense	Exon 13 of 14	NP_851607.2	Q8IZE3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCYL3	ENST00000367771.11	TSL:1 MANE Select	c.1723G>T	p.Gly575Trp	missense	Exon 12 of 13	ENSP00000356745.5	Q8IZE3-2
	SCYL3	ENST00000367770.5	TSL:1	c.1885G>T	p.Gly629Trp	missense	Exon 12 of 13	ENSP00000356744.1	Q8IZE3-1
	SCYL3	ENST00000910084.1		c.1924G>T	p.Gly642Trp	missense	Exon 14 of 15	ENSP00000580143.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251108 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461638 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 727126

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111932

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.050
DANN	Benign	0.55
DEOGEN2	Benign	0.00046	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.47
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.062
Sift	Benign	0.11	T
Sift4G	Uncertain	0.047	D
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.26		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.51
MPC		0.24
ClinPred		0.075	T
GERP RS		-11
Varity_R		0.014
gMVP		0.10
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1386750013; hg19: chr1-169823695;