chr13-77599712-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_144777.3(SCEL):āc.881T>Cā(p.Ile294Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,612,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.000023 ( 0 hom. )
Consequence
SCEL
NM_144777.3 missense
NM_144777.3 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 3.52
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.30351245).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCEL | NM_144777.3 | c.881T>C | p.Ile294Thr | missense_variant | 15/33 | ENST00000349847.4 | |
SCEL-AS1 | NR_126413.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCEL | ENST00000349847.4 | c.881T>C | p.Ile294Thr | missense_variant | 15/33 | 1 | NM_144777.3 | P2 | |
SCEL-AS1 | ENST00000457528.6 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251152Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135732
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1460148Hom.: 0 Cov.: 28 AF XY: 0.0000206 AC XY: 15AN XY: 726536
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74380
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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 submitter | clinical testing | Ambry Genetics | Jul 09, 2021 | The c.881T>C (p.I294T) alteration is located in exon 15 (coding exon 14) of the SCEL gene. This alteration results from a T to C substitution at nucleotide position 881, causing the isoleucine (I) at amino acid position 294 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;D;T
Sift4G
Uncertain
D;D;D
Polyphen
0.74, 1.0
.;P;D
Vest4
MVP
MPC
0.28
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at