Variant 13-77563871-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144777.3(SCEL):c.262C>T(p.Arg88Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,597,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SCEL
NM_144777.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.982

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 links:

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=0.17028302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCEL	NM_144777.3 linkuse as main transcript	c.262C>T	p.Arg88Trp	missense_variant	5/33	ENST00000349847.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCEL	ENST00000349847.4 linkuse as main transcript	c.262C>T	p.Arg88Trp	missense_variant	5/33	1	NM_144777.3	P2	O95171-1
SCEL	ENST00000377246.7 linkuse as main transcript	c.262C>T	p.Arg88Trp	missense_variant	5/32	1		A2	O95171-2
SCEL	ENST00000535157.5 linkuse as main transcript	c.262C>T	p.Arg88Trp	missense_variant	5/31	2		A2	O95171-3
SCEL	ENST00000471491.5 linkuse as main transcript	c.262C>T	p.Arg88Trp	missense_variant, NMD_transcript_variant	5/19	2

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

150842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000336

AC:

AN:

237788

Hom.:

AF XY:

0.0000545

AC XY:

AN XY:

128524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000948

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000576

Gnomad SAS exome

AF:

0.0000370

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1446942

Hom.:

Cov.:

AF XY:

0.0000250

AC XY:

AN XY:

719182

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.0000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000512

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000181

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000331

AC:

AN:

150842

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

73508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000499

Hom.:

ExAC

AF:

0.0000330

AC:

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

May 31, 2023

The c.262C>T (p.R88W) alteration is located in exon 5 (coding exon 4) of the SCEL gene. This alteration results from a C to T substitution at nucleotide position 262, causing the arginine (R) at amino acid position 88 to be replaced by a tryptophan (W). 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

-0.26

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.6

M;M;M

MutationTaster

Benign

0.63

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Benign

0.095

Sift

Benign

0.056

T;T;D

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.15

.;B;B

Vest4

0.37

MVP

0.28

MPC

0.055

ClinPred

0.84

GERP RS

2.4

Varity_R

0.11

gMVP

0.31

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over