Menu
GeneBe

13-77556703-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144777.3(SCEL):c.151G>A(p.Glu51Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,612,604 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 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SCEL
NM_144777.3 missense

Scores

3
5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07059705).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCELNM_144777.3 linkuse as main transcriptc.151G>A p.Glu51Lys missense_variant 3/33 ENST00000349847.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCELENST00000349847.4 linkuse as main transcriptc.151G>A p.Glu51Lys missense_variant 3/331 NM_144777.3 P2O95171-1
SCELENST00000377246.7 linkuse as main transcriptc.151G>A p.Glu51Lys missense_variant 3/321 A2O95171-2
SCELENST00000535157.5 linkuse as main transcriptc.151G>A p.Glu51Lys missense_variant 3/312 A2O95171-3
SCELENST00000471491.5 linkuse as main transcriptc.151G>A p.Glu51Lys missense_variant, NMD_transcript_variant 3/192

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
31
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000637
AC:
16
AN:
251172
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135750
show subpopulations
Gnomad AFR exome
AF:
0.000616
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1460306
Hom.:
0
Cov.:
29
AF XY:
0.0000138
AC XY:
10
AN XY:
726562
show subpopulations
Gnomad4 AFR exome
AF:
0.000598
Gnomad4 AMR exome
AF:
0.000157
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:
0.0000497
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.000698
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000134
Hom.:
0
Bravo
AF:
0.000185
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000741
AC:
9
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsMar 21, 2023The c.151G>A (p.E51K) alteration is located in exon 3 (coding exon 2) of the SCEL gene. This alteration results from a G to A substitution at nucleotide position 151, causing the glutamic acid (E) at amino acid position 51 to be replaced by a lysine (K). 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
0.15
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.33
Cadd
Pathogenic
27
Dann
Pathogenic
1.0
Eigen
Pathogenic
0.68
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.071
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
1.8
L;L;L
MutationTaster
Benign
0.80
D;D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-2.0
N;N;N
REVEL
Benign
0.13
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.020
D;D;D
Polyphen
1.0, 1.0
.;D;D
Vest4
0.46
MVP
0.44
MPC
0.35
ClinPred
0.18
T
GERP RS
5.3
Varity_R
0.57
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: rs139469817; hg19: chr13-78130838; API