1-152805445-G-T

Variant names:

• chr1-152805445-G-T
• rs1300829674
• NM_178351.4:c.34C>A

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.34C>A​(p.Pro12Thr) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LCE1C NM_178351.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.458
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE1C	NM_178351.4	c.34C>A	p.Pro12Thr	missense_variant	Exon 2 of 2	ENST00000607093.2	NP_848128.1
LCE1C	NM_001276331.2	c.34C>A	p.Pro12Thr	missense_variant	Exon 2 of 3		NP_001263260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE1C	ENST00000607093.2	c.34C>A	p.Pro12Thr	missense_variant	Exon 2 of 2	6	NM_178351.4	ENSP00000475270.1
LCE1C	ENST00000606576.1	c.34C>A	p.Pro12Thr	missense_variant	Exon 2 of 3	3		ENSP00000476034.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.34C>A (p.P12T) alteration is located in exon 2 (coding exon 1) of the LCE1C gene. This alteration results from a C to A substitution at nucleotide position 34, causing the proline (P) at amino acid position 12 to be replaced by a threonine (T). 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	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.097	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.47	T;.
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.9	M;.
PhyloP100		0.46
Sift4G	Uncertain	0.048	D;.
Polyphen		0.035	B;.
Vest4		0.25
MutPred		0.14		Gain of phosphorylation at P12 (P = 0.0085);Gain of phosphorylation at P12 (P = 0.0085);
MVP		0.32
ClinPred		0.14	T
GERP RS		2.1
Varity_R		0.69
gMVP		0.028
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: rs1300829674; hg19: chr1-152777921;