chr1-152566081-C-T

Variant names:

• chr1-152566081-C-T
• rs202162896
• NM_178435.4:c.128G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178435.4(LCE3E):​c.128G>A​(p.Gly43Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G43V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LCE3E NM_178435.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 0 publications found

Genes affected

LCE3E (HGNC:29463): (late cornified envelope 3E) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28966483).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178435.4. 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
	LCE3E	NM_178435.4	MANE Select	c.128G>A	p.Gly43Asp	missense	Exon 2 of 2	NP_848522.1	Q5T5B0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE3E	ENST00000368789.2	TSL:1 MANE Select	c.128G>A	p.Gly43Asp	missense	Exon 2 of 2	ENSP00000357778.1	Q5T5B0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461696 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727158

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44540

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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.026
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.30
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.064		Loss of glycosylation at S40 (P = 0.0678)
MVP		0.32
MPC		0.011
ClinPred		0.49	T
GERP RS		3.6
Varity_R		0.41
gMVP		0.029
Mutation Taster		=94/6	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: rs202162896; hg19: chr1-152538557;