chr13-77604412-C-T

Variant names:

• chr13-77604412-C-T
• rs147769726
• NM_144777.3:c.1154C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_144777.3(SCEL):​c.1154C>T​(p.Thr385Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,574,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SCEL NM_144777.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.995
• Publications: 2 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0490323).

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.1154C>T	p.Thr385Met	missense	Exon 19 of 33	NP_659001.2	O95171-1
	SCEL	NM_003843.4		c.1094C>T	p.Thr365Met	missense	Exon 18 of 32	NP_003834.3
	SCEL	NM_001160706.2		c.1031+1277C>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.1154C>T	p.Thr385Met	missense	Exon 19 of 33	ENSP00000302579.5	O95171-1
	SCEL	ENST00000377246.7	TSL:1	c.1094C>T	p.Thr365Met	missense	Exon 18 of 32	ENSP00000366454.3	O95171-2
	SCEL	ENST00000856158.1		c.1154C>T	p.Thr385Met	missense	Exon 19 of 33	ENSP00000526217.1

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151938 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000121 AC: 26 AN: 215066 AF XY: 0.000136

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000682

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000190

Gnomad OTH exome AF: 0.000393

GnomAD4 exome AF: 0.000120 AC: 171 AN: 1422168 Hom.: 0 Cov.: 29 AF XY: 0.000119 AC XY: 84 AN XY: 707704

African (AFR) AF: 0.00 AC: 0 AN: 30856

American (AMR) AF: 0.0000938 AC: 3 AN: 31976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24796

East Asian (EAS) AF: 0.0000265 AC: 1 AN: 37784

South Asian (SAS) AF: 0.00 AC: 0 AN: 78644

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53062

Middle Eastern (MID) AF: 0.000355 AC: 2 AN: 5628

European-Non Finnish (NFE) AF: 0.000144 AC: 159 AN: 1100812

Other (OTH) AF: 0.0000853 AC: 5 AN: 58610

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74342

African (AFR) AF: 0.0000482 AC: 2 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.0000982

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000989 AC: 12

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	0.099
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.99
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.045
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.047	D
Polyphen		0.16	B
Vest4		0.12
MVP		0.25
MPC		0.095
ClinPred		0.079	T
GERP RS		4.7
Varity_R		0.028
gMVP		0.20
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs147769726; hg19: chr13-78178547;