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GeneBe

13-77617648-A-C

Variant summary

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

The NM_144777.3(SCEL):c.1501A>C(p.Asn501His) 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. 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)

Consequence

SCEL
NM_144777.3 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46
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]

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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=0.18439925).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCELNM_144777.3 linkuse as main transcriptc.1501A>C p.Asn501His missense_variant 25/33 ENST00000349847.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCELENST00000349847.4 linkuse as main transcriptc.1501A>C p.Asn501His missense_variant 25/331 NM_144777.3 P2O95171-1
SCELENST00000377246.7 linkuse as main transcriptc.1441A>C p.Asn481His missense_variant 24/321 A2O95171-2
SCELENST00000535157.5 linkuse as main transcriptc.1375A>C p.Asn459His missense_variant 23/312 A2O95171-3
SCELENST00000469982.1 linkuse as main transcript downstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
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 GeneticsOct 25, 2022The c.1501A>C (p.N501H) alteration is located in exon 25 (coding exon 24) of the SCEL gene. This alteration results from a A to C substitution at nucleotide position 1501, causing the asparagine (N) at amino acid position 501 to be replaced by a histidine (H). 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
0.091
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
Cadd
Benign
18
Dann
Uncertain
0.99
Eigen
Benign
0.15
Eigen_PC
Benign
0.097
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.59
T;T;T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.075
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.031
D;T;D
Polyphen
0.73, 0.43
.;P;B
Vest4
0.21
MutPred
0.36
.;.;Gain of catalytic residue at N502 (P = 0.0597);
MVP
0.34
MPC
0.19
ClinPred
0.84
D
GERP RS
4.4
Varity_R
0.13
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: chr13-78191783; API