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GeneBe

13-77599712-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144777.3(SCEL):c.881T>C(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 (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SCEL
NM_144777.3 missense

Scores

7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52
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]
SCEL-AS1 (HGNC:39895): (SCEL antisense RNA 1)

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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
SCELNM_144777.3 linkuse as main transcriptc.881T>C p.Ile294Thr missense_variant 15/33 ENST00000349847.4
SCEL-AS1NR_126413.1 linkuse as main transcript downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCELENST00000349847.4 linkuse as main transcriptc.881T>C p.Ile294Thr missense_variant 15/331 NM_144777.3 P2O95171-1
SCEL-AS1ENST00000457528.6 linkuse as main transcript downstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
251152
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135732
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1460148
Hom.:
0
Cov.:
28
AF XY:
0.0000206
AC XY:
15
AN XY:
726536
show subpopulations
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:
0.0000279
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000533
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsJul 09, 2021The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.32
Cadd
Benign
23
Dann
Uncertain
1.0
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.30
T;T;T
MetaSVM
Benign
-0.83
T
MutationTaster
Benign
0.82
D;D;N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.4
N;N;N
REVEL
Benign
0.11
Sift
Benign
0.11
T;D;T
Sift4G
Uncertain
0.016
D;D;D
Polyphen
0.74, 1.0
.;P;D
Vest4
0.50
MVP
0.63
MPC
0.28
ClinPred
0.63
D
GERP RS
5.5
Varity_R
0.11
gMVP
0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201126612; hg19: chr13-78173847; API