1-152805268-C-T

Variant names:

• chr1-152805268-C-T
• rs150691692
• NM_178351.4:c.211G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178351.4(LCE1C):​c.211G>A​(p.Gly71Arg) 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. 11/18 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LCE1C NM_178351.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 0 publications found

Genes affected

LCE1C (HGNC:29464): (late cornified envelope 1C) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26642585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE1C	NM_178351.4	c.211G>A	p.Gly71Arg	missense_variant	Exon 2 of 2	ENST00000607093.2	NP_848128.1
LCE1C	NM_001276331.2	c.121G>A	p.Gly41Arg	missense_variant	Exon 3 of 3		NP_001263260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE1C	ENST00000607093.2	c.211G>A	p.Gly71Arg	missense_variant	Exon 2 of 2	6	NM_178351.4	ENSP00000475270.1
LCE1C	ENST00000606576.1	c.121G>A	p.Gly41Arg	missense_variant	Exon 3 of 3	3		ENSP00000476034.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.037	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.49	T;.
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		2.2
Sift4G	Uncertain	0.017	D;.
Polyphen		1.0	D;.
Vest4		0.30
MutPred		0.21		Gain of MoRF binding (P = 0.0087);.;
MVP		0.35
ClinPred		0.84	D
GERP RS		3.4
Varity_R		0.73
gMVP		0.016
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs150691692; hg19: chr1-152777744;