chr1-169855800-C-G

Variant names:

• chr1-169855800-C-G
• rs759769942
• ENST00000367770.5:c.1470G>C

Variant summary

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

The NM_181093.4(SCYL3):​c.1470G>C​(p.Gln490His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,459,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: SCYL3 NM_181093.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• 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]

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=0.12441763).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181093.4. 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
	SCYL3	NM_020423.7	MANE Select	c.1313-836G>C		intron	N/A	NP_065156.5
	SCYL3	NM_181093.4		c.1470G>C	p.Gln490His	missense	Exon 12 of 14	NP_851607.2	Q8IZE3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCYL3	ENST00000367770.5	TSL:1	c.1470G>C	p.Gln490His	missense	Exon 11 of 13	ENSP00000356744.1	Q8IZE3-1
	SCYL3	ENST00000367771.11	TSL:1 MANE Select	c.1313-836G>C		intron	N/A	ENSP00000356745.5	Q8IZE3-2
	SCYL3	ENST00000367772.8	TSL:2	c.1470G>C	p.Gln490His	missense	Exon 12 of 14	ENSP00000356746.4	Q8IZE3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249510 AF XY: 0.00000741

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: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000452 AC: 66 AN: 1459712 Hom.: 0 Cov.: 30 AF XY: 0.0000427 AC XY: 31 AN XY: 726142

African (AFR) AF: 0.0000300 AC: 1 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 85862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.0000513 AC: 57 AN: 1111124

Other (OTH) AF: 0.000133 AC: 8 AN: 60284

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.047
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.31
MutPred		0.37		Gain of loop (P = 0.0195)
MVP		0.53
MPC		0.19
ClinPred		0.16	T
GERP RS		3.1
Varity_R		0.094
gMVP		0.37
Mutation Taster		=97/3	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: rs759769942; hg19: chr1-169824941;