1-152805174-C-G

Variant names:

• chr1-152805174-C-G
• rs767707238
• NM_178351.4:c.305G>C

Variant summary

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

The NM_178351.4(LCE1C):​c.305G>C​(p.Gly102Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,460,460 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. 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. G102V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: LCE1C NM_178351.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22116432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE1C	NM_178351.4	c.305G>C	p.Gly102Ala	missense_variant	Exon 2 of 2	ENST00000607093.2	NP_848128.1
LCE1C	NM_001276331.2	c.215G>C	p.Gly72Ala	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.305G>C	p.Gly102Ala	missense_variant	Exon 2 of 2	6	NM_178351.4	ENSP00000475270.1
LCE1C	ENST00000606576.1	c.*52G>C		downstream_gene_variant		3		ENSP00000476034.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248166 AF XY: 0.00

Gnomad AFR exome AF: 0.0000660

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1460460 Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11 AN XY: 726446

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111366

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0062	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.4
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.22
MutPred		0.17		Loss of phosphorylation at S103 (P = 0.1775);
MVP		0.20
ClinPred		0.21	T
GERP RS		2.5
Varity_R		0.55
gMVP		0.029
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

Other links and lift over

dbSNP: rs767707238; hg19: chr1-152777650;