1-152776696-G-T

Position:

• chr1-152776696-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178354.3(LCE1F):​c.325G>T​(p.Gly109Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,432,794 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LCE1F NM_178354.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.336

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08496556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCE1F	NM_178354.3	c.325G>T	p.Gly109Cys	missense_variant	2/2	ENST00000334371.4	NP_848131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCE1F	ENST00000334371.4	c.325G>T	p.Gly109Cys	missense_variant	2/2	6	NM_178354.3	ENSP00000334187.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000355 AC: 8 AN: 225342 Hom.: 0 AF XY: 0.0000413 AC XY: 5 AN XY: 121014

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000442

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1432794 Hom.: 0 Cov.: 33 AF XY: 0.00000282 AC XY: 2 AN XY: 709394

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000760

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

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

Apr 18, 2023

The c.325G>T (p.G109C) alteration is located in exon 1 (coding exon 1) of the LCE1F gene. This alteration results from a G to T substitution at nucleotide position 325, causing the glycine (G) at amino acid position 109 to be replaced by a cysteine (C). 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	0.15
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.045
Sift4G	Benign	0.072	T
Polyphen		0.18	B
Vest4		0.31
MutPred		0.18		Loss of glycosylation at S110 (P = 0.0512);
MVP		0.22
MPC		0.057
ClinPred		0.091	T
GERP RS		3.2
Varity_R		0.69
gMVP		0.046

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

Publications

LitVar

Other links and lift over

dbSNP: rs776660451; hg19: chr1-152749172;