NM_178430.4:c.103C>T

Variant names:

• chr1-152664208-C-T
• rs768138746
• NM_178430.4:c.103C>T

Variant summary

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

The NM_178430.4(LCE2D):​c.103C>T​(p.Gln35*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LCE2D NM_178430.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.103C>T	p.Gln35*	stop_gained	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.103C>T	p.Gln35*	stop_gained	Exon 2 of 2	ENSP00000357773.1	Q5TA82
	ENSG00000304363	ENST00000802896.1		n.420+2353G>A		intron	N/A
	ENSG00000304363	ENST00000802897.1		n.234+2353G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

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: 8.99e-7 AC: 1 AN: 1112010

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
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	34
DANN	Benign	0.97
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.028	N
PhyloP100		0.57
Vest4		0.084
GERP RS		-5.4
Mutation Taster		=184/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs768138746; hg19: chr1-152636684;