1-152805235-G-A

Variant summary

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

The NM_178351.4(LCE1C):​c.244C>T​(p.Arg82Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

LCE1C
NM_178351.4 missense

Scores

15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

Publications

4 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LCE1CNM_178351.4 linkc.244C>T p.Arg82Cys missense_variant Exon 2 of 2 ENST00000607093.2 NP_848128.1 Q5T751
LCE1CNM_001276331.2 linkc.154C>T p.Arg52Cys missense_variant Exon 3 of 3 NP_001263260.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LCE1CENST00000607093.2 linkc.244C>T p.Arg82Cys missense_variant Exon 2 of 2 6 NM_178351.4 ENSP00000475270.1 Q5T751
LCE1CENST00000606576.1 linkc.154C>T p.Arg52Cys missense_variant Exon 3 of 3 3 ENSP00000476034.1 U3KQM4

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152090
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000280
AC:
7
AN:
249578
AF XY:
0.0000296
show subpopulations
Gnomad AFR exome
AF:
0.0000645
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461560
Hom.:
0
Cov.:
33
AF XY:
0.0000316
AC XY:
23
AN XY:
727092
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33464
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86240
European-Finnish (FIN)
AF:
0.0000374
AC:
2
AN:
53410
Middle Eastern (MID)
AF:
0.000181
AC:
1
AN:
5526
European-Non Finnish (NFE)
AF:
0.0000342
AC:
38
AN:
1112000
Other (OTH)
AF:
0.0000331
AC:
2
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
3
6
8
11
14
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
AF:
0.0000395
AC:
6
AN:
152090
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74288
show subpopulations
African (AFR)
AF:
0.0000483
AC:
2
AN:
41424
American (AMR)
AF:
0.00
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5178
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
0.0000942
AC:
1
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68006
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.433
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

Genome 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
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.244C>T (p.R82C) alteration is located in exon 2 (coding exon 1) of the LCE1C gene. This alteration results from a C to T substitution at nucleotide position 244, causing the arginine (R) at amino acid position 82 to be replaced by a cysteine (C). 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
Benign
0.11
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
22
DANN
Benign
0.66
DEOGEN2
Benign
0.0088
T;.
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.072
N
LIST_S2
Benign
0.46
T;.
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.057
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.2
L;.
PhyloP100
1.3
Sift4G
Benign
0.15
T;.
Polyphen
0.96
D;.
Vest4
0.26
MVP
0.12
ClinPred
0.068
T
GERP RS
1.7
Varity_R
0.62
gMVP
0.034
Mutation Taster
=97/3
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.44
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.44
Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs771441994; hg19: chr1-152777711; COSMIC: COSV64218856; API