chr1-152798087-G-A

Position:

• chr1-152798087-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178352.3(LCE1D):​c.293G>A​(p.Gly98Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 1,291,212 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 23)
  • Exomes 𝑓: 0.0000023 (1 hom.)
• Consequence: LCE1D NM_178352.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.870

Genes affected

LCE1D (HGNC:29465): (late cornified envelope 1D) Enables identical protein binding activity. Involved in cognition. Acts upstream of or within cellular response to calcium ion. Located in cornified envelope and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33537942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCE1D	NM_178352.3	c.293G>A	p.Gly98Asp	missense_variant	2/2	ENST00000326233.7	NP_848129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCE1D	ENST00000326233.7	c.293G>A	p.Gly98Asp	missense_variant	2/2	5	NM_178352.3	ENSP00000316737.6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000232 AC: 3 AN: 1291212 Hom.: 1 Cov.: 32 AF XY: 0.00000312 AC XY: 2 AN XY: 641818

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000239

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000207

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

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

Oct 29, 2024

The c.293G>A (p.G98D) alteration is located in exon 2 (coding exon 1) of the LCE1D gene. This alteration results from a G to A substitution at nucleotide position 293, causing the glycine (G) at amino acid position 98 to be replaced by an aspartic acid (D). 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	0.18
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.075
Sift4G	Uncertain	0.014	D
Polyphen		0.94	P
Vest4		0.41
MutPred		0.19		Loss of catalytic residue at G98 (P = 0.1537);
MVP		0.43
MPC		0.38
ClinPred		0.86	D
GERP RS		4.3
Varity_R		0.84
gMVP		0.027

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: rs1255521869; hg19: chr1-152770563;