rs147545899

Variant names:

• chr13-77572141-C-T
• rs147545899
• NM_144777.3:c.497C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-77572141-C-T
• chr13-77572141-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_144777.3(SCEL):​c.497C>T​(p.Pro166Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000105 in 1,612,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: SCEL NM_144777.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• Publications: 6 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]

ENSG00000287270 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1917552).

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.497C>T	p.Pro166Leu	missense	Exon 9 of 33	NP_659001.2	O95171-1
	SCEL	NM_003843.4		c.497C>T	p.Pro166Leu	missense	Exon 9 of 32	NP_003834.3
	SCEL	NM_001160706.2		c.479+2690C>T		intron	N/A	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.497C>T	p.Pro166Leu	missense	Exon 9 of 33	ENSP00000302579.5	O95171-1
	SCEL	ENST00000377246.7	TSL:1	c.497C>T	p.Pro166Leu	missense	Exon 9 of 32	ENSP00000366454.3	O95171-2
	SCEL	ENST00000856158.1		c.497C>T	p.Pro166Leu	missense	Exon 9 of 33	ENSP00000526217.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000116 AC: 29 AN: 250544 AF XY: 0.000126

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000959 AC: 140 AN: 1460280 Hom.: 0 Cov.: 29 AF XY: 0.000105 AC XY: 76 AN XY: 726466

African (AFR) AF: 0.0000599 AC: 2 AN: 33374

American (AMR) AF: 0.0000448 AC: 2 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 86106

European-Finnish (FIN) AF: 0.0000750 AC: 4 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000113 AC: 125 AN: 1111024

Other (OTH) AF: 0.0000994 AC: 6 AN: 60344

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74428

African (AFR) AF: 0.000289 AC: 12 AN: 41540

American (AMR) AF: 0.000261 AC: 4 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000166 Hom.: 0

Bravo AF: 0.000174

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000164

EpiControl AF: 0.000238

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	0.29
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.6
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.39
MVP		0.37
MPC		0.34
ClinPred		0.44	T
GERP RS		5.2
Varity_R		0.46
gMVP		0.32
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs147545899; hg19: chr13-78146276;