Variant chr13-77591448-A-G 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.680A>G(p.Glu227Gly) 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. 13/21 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCEL
NM_144777.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

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:

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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=0.16554505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCEL	NM_144777.3 linkuse as main transcript	c.680A>G	p.Glu227Gly	missense_variant	11/33	ENST00000349847.4	NP_659001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCEL	ENST00000349847.4 linkuse as main transcript	c.680A>G	p.Glu227Gly	missense_variant	11/33	1	NM_144777.3	ENSP00000302579	P2	O95171-1
SCEL	ENST00000377246.7 linkuse as main transcript	c.680A>G	p.Glu227Gly	missense_variant	11/32	1		ENSP00000366454	A2	O95171-2
SCEL	ENST00000535157.5 linkuse as main transcript	c.614A>G	p.Glu205Gly	missense_variant	10/31	2		ENSP00000437895	A2	O95171-3
SCEL	ENST00000471491.5 linkuse as main transcript	c.611A>G	p.Glu204Gly	missense_variant, NMD_transcript_variant	10/19	2		ENSP00000432840

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1407566

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703396

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 17, 2021

The c.680A>G (p.E227G) alteration is located in exon 11 (coding exon 10) of the SCEL gene. This alteration results from a A to G substitution at nucleotide position 680, causing the glutamic acid (E) at amino acid position 227 to be replaced by a glycine (G). 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

0.14

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

.;.;T

Eigen

Benign

-0.030

Eigen_PC

Benign

-0.097

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;M;M

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.043

D;D;D

Sift4G

Benign

0.33

T;T;D

Polyphen

0.82, 0.91

.;P;P

Vest4

0.33

MutPred

0.26

.;Gain of catalytic residue at R228 (P = 0.0219);Gain of catalytic residue at R228 (P = 0.0219);

MVP

0.24

MPC

0.30

ClinPred

0.87

GERP RS

2.4

Varity_R

0.10

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over