rs140695935

Variant names:

• chr13-77555907-C-G
• NM_144777.3:c.32C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-77555907-C-G
• chr13-77555907-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144777.3(SCEL):​c.32C>G​(p.Pro11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCEL NM_144777.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21122739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCEL	NM_144777.3	c.32C>G	p.Pro11Arg	missense_variant	Exon 2 of 33	ENST00000349847.4	NP_659001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCEL	ENST00000349847.4	c.32C>G	p.Pro11Arg	missense_variant	Exon 2 of 33	1	NM_144777.3	ENSP00000302579.5
SCEL	ENST00000377246.7	c.32C>G	p.Pro11Arg	missense_variant	Exon 2 of 32	1		ENSP00000366454.3
SCEL	ENST00000535157.5	c.32C>G	p.Pro11Arg	missense_variant	Exon 2 of 31	2		ENSP00000437895.1
SCEL	ENST00000471491.5	n.32C>G		non_coding_transcript_exon_variant	Exon 2 of 19	2		ENSP00000432840.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461172 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726930

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	.;.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.5	L;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.22
MutPred		0.20		Gain of solvent accessibility (P = 0.0216);Gain of solvent accessibility (P = 0.0216);Gain of solvent accessibility (P = 0.0216);
MVP		0.33
MPC		0.29
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.096

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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: chr13-78130042;