rs8002725

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-77613943-A-C
• chr13-77613943-A-G

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.1439A>C​(p.Lys480Thr) 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. 14/22 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: not found (cov: 32)
• 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: 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=0.2019059).

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>C	p.Lys480Thr	missense	Exon 24 of 33	NP_659001.2
	SCEL	NM_003843.4		c.1379A>C	p.Lys460Thr	missense	Exon 23 of 32	NP_003834.3
	SCEL	NM_001160706.2		c.1313A>C	p.Lys438Thr	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>C	p.Lys480Thr	missense	Exon 24 of 33	ENSP00000302579.5
	SCEL	ENST00000377246.7	TSL:1	c.1379A>C	p.Lys460Thr	missense	Exon 23 of 32	ENSP00000366454.3
	SCEL	ENST00000856158.1		c.1436A>C	p.Lys479Thr	missense	Exon 24 of 33	ENSP00000526217.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0059	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.60	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.20	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.4
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.18
Sift	Benign	0.065	T
Sift4G	Benign	0.31	T
Polyphen		0.45	B
Vest4		0.24
MutPred		0.28		Gain of catalytic residue at N481 (P = 0.011)
MVP		0.76
MPC		0.13
ClinPred		0.50	D
GERP RS		3.9
Varity_R		0.069
gMVP		0.39
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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;