1-169854607-T-G

Position:

• chr1-169854607-T-G

Variant summary

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

The NM_020423.7(SCYL3):​c.1670A>C​(p.Glu557Ala) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCYL3 NM_020423.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057932943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCYL3	NM_020423.7	c.1670A>C	p.Glu557Ala	missense_variant	12/13	ENST00000367771.11	NP_065156.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCYL3	ENST00000367771.11	c.1670A>C	p.Glu557Ala	missense_variant	12/13	1	NM_020423.7	ENSP00000356745.5
SCYL3	ENST00000367770.5	c.1832A>C	p.Glu611Ala	missense_variant	12/13	1		ENSP00000356744.1
SCYL3	ENST00000367772.8	c.1832A>C	p.Glu611Ala	missense_variant	13/14	2		ENSP00000356746.4
SCYL3	ENST00000423670.1	c.1670A>C	p.Glu557Ala	missense_variant	12/12	5		ENSP00000407993.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.1832A>C (p.E611A) alteration is located in exon 13 (coding exon 12) of the SCYL3 gene. This alteration results from a A to C substitution at nucleotide position 1832, causing the glutamic acid (E) at amino acid position 611 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0079	.;T;T;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.69	T;.;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.058	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;M;M;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.068
Sift	Benign	0.15	T;T;T;T
Sift4G	Benign	0.14	T;T;T;.
Polyphen		0.26	B;B;B;.
Vest4		0.15
MutPred		0.28		.;Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);.;
MVP		0.39
MPC		0.21
ClinPred		0.16	T
GERP RS		3.0
Varity_R		0.048
gMVP		0.21

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: chr1-169823748;