1-152805247-T-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.232A>C​(p.Ser78Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

LCE1C
NM_178351.4 missense

Scores

1
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.688

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=0.079919994).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LCE1CNM_178351.4 linkc.232A>C p.Ser78Arg missense_variant Exon 2 of 2 ENST00000607093.2 NP_848128.1 Q5T751
LCE1CNM_001276331.2 linkc.142A>C p.Ser48Arg 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.232A>C p.Ser78Arg missense_variant Exon 2 of 2 6 NM_178351.4 ENSP00000475270.1 Q5T751
LCE1CENST00000606576.1 linkc.142A>C p.Ser48Arg missense_variant Exon 3 of 3 3 ENSP00000476034.1 U3KQM4

Frequencies

GnomAD3 genomes
AF:
0.0000855
AC:
13
AN:
152034
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000919
AC:
23
AN:
250136
AF XY:
0.0000812
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000186
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000705
AC:
103
AN:
1461652
Hom.:
0
Cov.:
33
AF XY:
0.0000674
AC XY:
49
AN XY:
727130
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33474
American (AMR)
AF:
0.0000671
AC:
3
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86246
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5586
European-Non Finnish (NFE)
AF:
0.0000872
AC:
97
AN:
1112000
Other (OTH)
AF:
0.0000497
AC:
3
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
8
15
23
30
38
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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:
0.0000854
AC:
13
AN:
152152
Hom.:
0
Cov.:
31
AF XY:
0.0000941
AC XY:
7
AN XY:
74376
show subpopulations
African (AFR)
AF:
0.0000482
AC:
2
AN:
41508
American (AMR)
AF:
0.0000654
AC:
1
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5164
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4806
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10586
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000147
AC:
10
AN:
68012
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
1
2
4
5
6
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:
0.0000680
Hom.:
0
Bravo
AF:
0.0000793
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 26, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.232A>C (p.S78R) alteration is located in exon 2 (coding exon 1) of the LCE1C gene. This alteration results from a A to C substitution at nucleotide position 232, causing the serine (S) at amino acid position 78 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
0.78
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.019
T;.
Eigen
Benign
0.18
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.44
T;.
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.080
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;.
PhyloP100
0.69
Sift4G
Benign
0.090
T;.
Polyphen
0.78
P;.
Vest4
0.49
MutPred
0.19
Gain of MoRF binding (P = 0.0137);.;
MVP
0.32
ClinPred
0.13
T
GERP RS
2.1
Varity_R
0.81
gMVP
0.031
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs202080650; hg19: chr1-152777723; COSMIC: COSV64219307; API