rs200214247

Variant names:

• chr1-169854690-G-C
• rs200214247
• NM_020423.7:c.1587C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020423.7(SCYL3):​c.1587C>G​(p.Asn529Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,614,000 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000078 (0 hom.)
• Consequence: SCYL3 NM_020423.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.554
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03860858).

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.1587C>G	p.Asn529Lys	missense	Exon 12 of 13	NP_065156.5
	SCYL3	NM_181093.4		c.1749C>G	p.Asn583Lys	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.1587C>G	p.Asn529Lys	missense	Exon 12 of 13	ENSP00000356745.5	Q8IZE3-2
	SCYL3	ENST00000367770.5	TSL:1	c.1749C>G	p.Asn583Lys	missense	Exon 12 of 13	ENSP00000356744.1	Q8IZE3-1
	SCYL3	ENST00000910084.1		c.1788C>G	p.Asn596Lys	missense	Exon 14 of 15	ENSP00000580143.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152110 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000478 AC: 12 AN: 250942 AF XY: 0.0000516

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000780 AC: 114 AN: 1461772 Hom.: 0 Cov.: 34 AF XY: 0.0000701 AC XY: 51 AN XY: 727202

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.000179 AC: 8 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000926 AC: 103 AN: 1111934

Other (OTH) AF: 0.0000497 AC: 3 AN: 60392

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152228 Hom.: 1 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74422

African (AFR) AF: 0.00 AC: 0 AN: 41538

American (AMR) AF: 0.000851 AC: 13 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.000121

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000494 AC: 6

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	0.10
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.9
DANN	Benign	0.80
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.55
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.053
Sift	Benign	0.042	D
Sift4G	Benign	0.085	T
Polyphen		0.10	B
Vest4		0.090
MutPred		0.38		Gain of ubiquitination at N583 (P = 0.0025)
MVP		0.24
MPC		0.25
ClinPred		0.035	T
GERP RS		-0.15
Varity_R		0.035
gMVP		0.11
Mutation Taster		=92/8	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: rs200214247; hg19: chr1-169823831;