1-152664163-T-A

Variant names:

• chr1-152664163-T-A
• NM_178430.4:c.58T>A
• LCE2D p.Cys20Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178430.4(LCE2D):​c.58T>A​(p.Cys20Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C20Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCE2D NM_178430.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39
• Publications: 0 publications found

Genes affected

LCE2D (HGNC:16518): (late cornified envelope 2D) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000304363 (HGNC:):

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=0.26328316).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178430.4. 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
	LCE2D	NM_178430.4	MANE Select	c.58T>A	p.Cys20Ser	missense	Exon 2 of 2	NP_848517.1	Q5TA82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE2D	ENST00000368784.2	TSL:1 MANE Select	c.58T>A	p.Cys20Ser	missense	Exon 2 of 2	ENSP00000357773.1	Q5TA82
	ENSG00000304363	ENST00000802896.1		n.420+2398A>T		intron	N/A
	ENSG00000304363	ENST00000802897.1		n.234+2398A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.45
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.00048
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.4
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.070
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.039	D
Varity_R		0.48
gMVP		0.029
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-152636639;