1-152664257-G-C

Variant names:

• chr1-152664257-G-C
• rs771895548
• NM_178430.4:c.152G>C

Variant summary

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

The NM_178430.4(LCE2D):​c.152G>C​(p.Ser51Thr) 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. 14/21 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. S51I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCE2D NM_178430.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769
• Publications: 0 publications found

Genes affected

LCE2D (HGNC:16518): (late cornified envelope 2D) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000304363 (HGNC:):

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=0.16638383).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178430.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE2D	NM_178430.4	MANE Select	c.152G>C	p.Ser51Thr	missense	Exon 2 of 2	NP_848517.1	Q5TA82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE2D	ENST00000368784.2	TSL:1 MANE Select	c.152G>C	p.Ser51Thr	missense	Exon 2 of 2	ENSP00000357773.1	Q5TA82
	ENSG00000304363	ENST00000802896.1		n.420+2304C>G		intron	N/A
	ENSG00000304363	ENST00000802897.1		n.234+2304C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.7
DANN	Benign	0.23
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.77
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.082
Sift	Benign	0.92	T
Sift4G	Benign	0.096	T
Polyphen		0.93	P
Vest4		0.25
MutPred		0.12		Gain of glycosylation at S51 (P = 0.0362)
MVP		0.22
MPC		0.0045
ClinPred		0.11	T
GERP RS		1.5
Varity_R		0.18
gMVP		0.031
Mutation Taster		=100/0	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: rs771895548; hg19: chr1-152636733;