chr1-152776424-C-T

Variant names:

• chr1-152776424-C-T
• rs1651598499
• NM_178354.3:c.53C>T

Variant summary

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

The NM_178354.3(LCE1F):​c.53C>T​(p.Pro18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LCE1F NM_178354.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11
• Publications: 0 publications found

Genes affected

LCE1F (HGNC:29467): (late cornified envelope 1F) Enables identical protein binding activity. Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

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_178354.3. 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
	LCE1F	NM_178354.3	MANE Select	c.53C>T	p.Pro18Leu	missense	Exon 2 of 2	NP_848131.1	Q5T754

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE1F	ENST00000334371.4	TSL:6 MANE Select	c.53C>T	p.Pro18Leu	missense	Exon 2 of 2	ENSP00000334187.2	Q5T754

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33462

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: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

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: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Benign	0.90
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0050	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		3.1
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.088
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.14		Loss of glycosylation at P18 (P = 0.0036)
MVP		0.29
MPC		0.055
ClinPred		0.94	D
GERP RS		4.4
Varity_R		0.64
gMVP		0.027
Mutation Taster		=88/12	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: rs1651598499; hg19: chr1-152748900;