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GeneBe

13-77591448-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_144777.3(SCEL):c.680A>G(p.Glu227Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SCEL
NM_144777.3 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08
Variant links:
Genes affected
SCEL (HGNC:10573): (sciellin) The protein encoded by this gene is a precursor to the cornified envelope of terminally differentiated keratinocytes. This protein localizes to the periphery of cells and may function in the assembly or regulation of proteins in the cornified envelope. Transcript variants encoding different isoforms exist. A transcript variant utilizing an alternative polyA signal has been described in the literature, but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16554505).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCELNM_144777.3 linkuse as main transcriptc.680A>G p.Glu227Gly missense_variant 11/33 ENST00000349847.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCELENST00000349847.4 linkuse as main transcriptc.680A>G p.Glu227Gly missense_variant 11/331 NM_144777.3 P2O95171-1
SCELENST00000377246.7 linkuse as main transcriptc.680A>G p.Glu227Gly missense_variant 11/321 A2O95171-2
SCELENST00000535157.5 linkuse as main transcriptc.614A>G p.Glu205Gly missense_variant 10/312 A2O95171-3
SCELENST00000471491.5 linkuse as main transcriptc.611A>G p.Glu204Gly missense_variant, NMD_transcript_variant 10/192

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1407566
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
703396
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 17, 2021The c.680A>G (p.E227G) alteration is located in exon 11 (coding exon 10) of the SCEL gene. This alteration results from a A to G substitution at nucleotide position 680, causing the glutamic acid (E) at amino acid position 227 to be replaced by a glycine (G). 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
0.14
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Benign
-0.31
Cadd
Benign
22
Dann
Uncertain
0.99
Eigen
Benign
-0.030
Eigen_PC
Benign
-0.097
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.99
N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.12
Sift
Benign
0.043
D;D;D
Sift4G
Benign
0.33
T;T;D
Polyphen
0.82, 0.91
.;P;P
Vest4
0.33
MutPred
0.26
.;Gain of catalytic residue at R228 (P = 0.0219);Gain of catalytic residue at R228 (P = 0.0219);
MVP
0.24
MPC
0.30
ClinPred
0.87
D
GERP RS
2.4
Varity_R
0.10
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr13-78165583; API