1-169855858-C-T

Position:

• chr1-169855858-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_181093.4(SCYL3):​c.1412G>A​(p.Ser471Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCYL3 NM_181093.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04244238).
• BP6: Variant 1-169855858-C-T is Benign according to our data. Variant chr1-169855858-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2243424.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCYL3	NM_020423.7	c.1313-894G>A		intron_variant		ENST00000367771.11	NP_065156.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCYL3	ENST00000367770.5	c.1412G>A	p.Ser471Asn	missense_variant	11/13	1		ENSP00000356744.1
SCYL3	ENST00000367771.11	c.1313-894G>A		intron_variant		1	NM_020423.7	ENSP00000356745.5
SCYL3	ENST00000367772.8	c.1412G>A	p.Ser471Asn	missense_variant	12/14	2		ENSP00000356746.4
SCYL3	ENST00000423670.1	c.1313-894G>A		intron_variant		5		ENSP00000407993.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.85
DEOGEN2	Benign	0.0029	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.33	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.21	N;N
REVEL	Benign	0.060
Sift	Benign	0.40	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0	B;B
Vest4		0.064
MutPred		0.34		Loss of helix (P = 0.0123);Loss of helix (P = 0.0123);
MVP		0.24
MPC		0.18
ClinPred		0.26	T
GERP RS		-4.7
Varity_R		0.044
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-169824999; COSMIC: COSV53681225; COSMIC: COSV53681225;