13-77613943-A-G

Variant names:

• chr13-77613943-A-G
• rs8002725
• NM_144777.3:c.1439A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4051 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21895 hom.)
• Consequence: SCEL NM_144777.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 23 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: Benign. The variant received -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.

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.1439A>G	p.Lys480Arg	missense	Exon 24 of 33	NP_659001.2
	SCEL	NM_003843.4		c.1379A>G	p.Lys460Arg	missense	Exon 23 of 32	NP_003834.3
	SCEL	NM_001160706.2		c.1313A>G	p.Lys438Arg	missense	Exon 22 of 31	NP_001154178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCEL	ENST00000349847.4	TSL:1 MANE Select	c.1439A>G	p.Lys480Arg	missense	Exon 24 of 33	ENSP00000302579.5
	SCEL	ENST00000377246.7	TSL:1	c.1379A>G	p.Lys460Arg	missense	Exon 23 of 32	ENSP00000366454.3
	SCEL	ENST00000856158.1		c.1436A>G	p.Lys479Arg	missense	Exon 24 of 33	ENSP00000526217.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31437 AN: 151978 Hom.: 4050 Cov.: 32

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

GnomAD2 exomes AF: 0.166 AC: 41594 AN: 250316 AF XY: 0.162

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 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.: 30 AF XY: 0.166 AC XY: 120207 AN XY: 725752

African (AFR) AF: 0.364 AC: 12115 AN: 33272

American (AMR) AF: 0.200 AC: 8917 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 2475 AN: 26100

East Asian (EAS) AF: 0.164 AC: 6490 AN: 39626

South Asian (SAS) AF: 0.181 AC: 15567 AN: 86016

European-Finnish (FIN) AF: 0.0879 AC: 4695 AN: 53406

Middle Eastern (MID) AF: 0.110 AC: 636 AN: 5760

European-Non Finnish (NFE) AF: 0.164 AC: 182441 AN: 1109732

Other (OTH) AF: 0.167 AC: 10041 AN: 60276

GnomAD4 genome AF: 0.207 AC: 31478 AN: 152096 Hom.: 4051 Cov.: 32 AF XY: 0.204 AC XY: 15192 AN XY: 74348

African (AFR) AF: 0.359 AC: 14896 AN: 41474

American (AMR) AF: 0.188 AC: 2868 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 313 AN: 3472

East Asian (EAS) AF: 0.144 AC: 745 AN: 5180

South Asian (SAS) AF: 0.188 AC: 910 AN: 4828

European-Finnish (FIN) AF: 0.0834 AC: 885 AN: 10608

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10305 AN: 67976

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.168 Hom.: 8359

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.4
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.10
Sift	Benign	0.32	T
Sift4G	Benign	0.23	T
Polyphen		0.0030	B
Vest4		0.059
MPC		0.045
ClinPred		0.0051	T
GERP RS		3.9
Varity_R		0.036
gMVP		0.21
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8002725; hg19: chr13-78188078; COSMIC: COSV62993129; COSMIC: COSV62993129;