1-152805472-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178351.4(LCE1C):​c.7T>C​(p.Cys3Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LCE1C
NM_178351.4 missense

Scores

3
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

Publications

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.236608).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LCE1CNM_178351.4 linkc.7T>C p.Cys3Arg missense_variant Exon 2 of 2 ENST00000607093.2 NP_848128.1 Q5T751
LCE1CNM_001276331.2 linkc.7T>C p.Cys3Arg missense_variant Exon 2 of 3 NP_001263260.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LCE1CENST00000607093.2 linkc.7T>C p.Cys3Arg missense_variant Exon 2 of 2 6 NM_178351.4 ENSP00000475270.1 Q5T751
LCE1CENST00000606576.1 linkc.7T>C p.Cys3Arg missense_variant Exon 2 of 3 3 ENSP00000476034.1 U3KQM4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251112
AF XY:
0.00000737
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461718
Hom.:
0
Cov.:
40
AF XY:
0.00000275
AC XY:
2
AN XY:
727176
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33468
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111878
Other (OTH)
AF:
0.00
AC:
0
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 25, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.7T>C (p.C3R) alteration is located in exon 2 (coding exon 1) of the LCE1C gene. This alteration results from a T to C substitution at nucleotide position 7, causing the cysteine (C) at amino acid position 3 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.79
BayesDel_addAF
Uncertain
0.060
T
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
24
DANN
Benign
0.90
DEOGEN2
Benign
0.10
T;.
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.32
T;.
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.0
M;.
PhyloP100
4.3
Sift4G
Pathogenic
0.0010
D;.
Polyphen
0.98
D;.
Vest4
0.75
MutPred
0.20
Loss of catalytic residue at M1 (P = 2e-04);Loss of catalytic residue at M1 (P = 2e-04);
MVP
0.37
ClinPred
0.69
D
GERP RS
3.5
Varity_R
0.89
gMVP
0.0098
Mutation Taster
=96/4
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

Publications

Other links and lift over

dbSNP: rs1346724469; hg19: chr1-152777948; API