chr13-77563871-C-T

Variant names:

• chr13-77563871-C-T
• rs760072376
• NM_144777.3:c.262C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R88Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: SCEL NM_144777.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.982
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17028302).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144777.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCEL	NM_144777.3	MANE Select	c.262C>T	p.Arg88Trp	missense	Exon 5 of 33	NP_659001.2	O95171-1
	SCEL	NM_003843.4		c.262C>T	p.Arg88Trp	missense	Exon 5 of 32	NP_003834.3
	SCEL	NM_001160706.2		c.262C>T	p.Arg88Trp	missense	Exon 5 of 31	NP_001154178.1	O95171-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCEL	ENST00000349847.4	TSL:1 MANE Select	c.262C>T	p.Arg88Trp	missense	Exon 5 of 33	ENSP00000302579.5	O95171-1
	SCEL	ENST00000377246.7	TSL:1	c.262C>T	p.Arg88Trp	missense	Exon 5 of 32	ENSP00000366454.3	O95171-2
	SCEL	ENST00000856158.1		c.262C>T	p.Arg88Trp	missense	Exon 5 of 33	ENSP00000526217.1

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 5 AN: 150842 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.0000336 AC: 8 AN: 237788 AF XY: 0.0000545

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 29 AN: 1446942 Hom.: 0 Cov.: 30 AF XY: 0.0000250 AC XY: 18 AN XY: 719182

African (AFR) AF: 0.0000307 AC: 1 AN: 32540

American (AMR) AF: 0.0000716 AC: 3 AN: 41878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25794

East Asian (EAS) AF: 0.0000512 AC: 2 AN: 39062

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5708

European-Non Finnish (NFE) AF: 0.0000181 AC: 20 AN: 1106890

Other (OTH) AF: 0.0000167 AC: 1 AN: 59726

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 150842 Hom.: 0 Cov.: 32 AF XY: 0.0000680 AC XY: 5 AN XY: 73508

African (AFR) AF: 0.00 AC: 0 AN: 40994

American (AMR) AF: 0.0000661 AC: 1 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67860

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.0000499 Hom.: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.98
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.095
Sift	Benign	0.056	T
Sift4G	Uncertain	0.030	D
Polyphen		0.15	B
Vest4		0.37
MVP		0.28
MPC		0.055
ClinPred		0.84	D
GERP RS		2.4
Varity_R		0.11
gMVP		0.31
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs760072376; hg19: chr13-78138006;