Variant 13-77613943-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144777.3(SCEL):c.1439A>G(p.Lys480Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,610,804 control chromosomes in the GnomAD database, including 25,946 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 4051 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21895 hom. )

Consequence

SCEL
NM_144777.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.37

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:

SCEL (HGNC:):

SCEL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048075616).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCEL	NM_144777.3 linkuse as main transcript	c.1439A>G	p.Lys480Arg	missense_variant	24/33	ENST00000349847.4	NP_659001.2	O95171-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCEL	ENST00000349847.4 linkuse as main transcript	c.1439A>G	p.Lys480Arg	missense_variant	24/33	1	NM_144777.3	ENSP00000302579.5	O95171-1
SCEL	ENST00000377246.7 linkuse as main transcript	c.1379A>G	p.Lys460Arg	missense_variant	23/32	1		ENSP00000366454.3	O95171-2
SCEL	ENST00000535157.5 linkuse as main transcript	c.1313A>G	p.Lys438Arg	missense_variant	22/31	2		ENSP00000437895.1	O95171-3
SCEL	ENST00000469982.1 linkuse as main transcript	n.535A>G		non_coding_transcript_exon_variant	9/10	5

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31437

AN:

151978

Hom.:

4050

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.0901

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.0834

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.197

GnomAD3 exomes

AF:

0.166

AC:

41594

AN:

250316

Hom.:

4013

AF XY:

0.162

AC XY:

21954

AN XY:

135282

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.0955

Gnomad EAS exome

AF:

0.144

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.0829

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.167

AC:

243377

AN:

1458708

Hom.:

21895

Cov.:

AF XY:

0.166

AC XY:

120207

AN XY:

725752

show subpopulations

Gnomad4 AFR exome

AF:

0.364

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.0948

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.0879

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.207

AC:

31478

AN:

152096

Hom.:

4051

Cov.:

AF XY:

0.204

AC XY:

15192

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.359

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.0901

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.0834

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.158

Hom.:

5043

Bravo

AF:

0.222

TwinsUK

AF:

0.164

AC:

608

ALSPAC

AF:

0.175

AC:

675

ESP6500AA

AF:

0.355

AC:

1565

ESP6500EA

AF:

0.149

AC:

1284

ExAC

AF:

0.170

AC:

20625

Asia WGS

AF:

0.199

AC:

689

AN:

3474

EpiCase

AF:

0.149

EpiControl

AF:

0.144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.025

.;.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.51

T;T;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;.;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.32

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.23

T;D;T

Polyphen

0.0030, 0.0010

.;B;B

Vest4

0.059

MPC

0.045

ClinPred

0.0051

GERP RS

3.9

Varity_R

0.036

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over