1-152676100-C-G

Position:

• chr1-152676100-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000368783.2(LCE2C):​c.85C>G​(p.Pro29Ala) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P29L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCE2C ENST00000368783.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

Genes affected

LCE2C (HGNC:29460): (late cornified envelope 2C) Enables identical protein binding activity. Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06504223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCE2C	NM_178429.5	c.85C>G	p.Pro29Ala	missense_variant	2/2	ENST00000368783.2	NP_848516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCE2C	ENST00000368783.2	c.85C>G	p.Pro29Ala	missense_variant	2/2	1	NM_178429.5	ENSP00000357772	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2022

The c.85C>G (p.P29A) alteration is located in exon 2 (coding exon 1) of the LCE2C gene. This alteration results from a C to G substitution at nucleotide position 85, causing the proline (P) at amino acid position 29 to be replaced by an alanine (A). 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	0.082
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.8
DANN	Benign	0.71
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.2	M
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.040
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.082	T
Polyphen		0.015	B
Vest4		0.27
MutPred		0.27		Loss of glycosylation at P29 (P = 0.0046);
MVP		0.13
MPC		0.0034
ClinPred		0.28	T
GERP RS		2.2
Varity_R		0.089
gMVP		0.026

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-152648576;