rs147769726

Variant names:

• chr13-77604412-C-G
• NM_144777.3:c.1154C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-77604412-C-G
• chr13-77604412-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144777.3(SCEL):​c.1154C>G​(p.Thr385Arg) 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. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T385M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCEL NM_144777.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.995

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-AS1 (HGNC:39895): (SCEL antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCEL	NM_144777.3	c.1154C>G	p.Thr385Arg	missense_variant	Exon 19 of 33	ENST00000349847.4	NP_659001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCEL	ENST00000349847.4	c.1154C>G	p.Thr385Arg	missense_variant	Exon 19 of 33	1	NM_144777.3	ENSP00000302579.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.027	.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.065	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	.;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.67	N;N
REVEL	Benign	0.041
Sift	Benign	0.74	T;T
Sift4G	Benign	0.82	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.21		.;Gain of MoRF binding (P = 0.0157);
MVP		0.20
MPC		0.055
ClinPred		0.25	T
GERP RS		4.7
Varity_R		0.046
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.26		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-78178547;