1-152798041-C-G

Variant names:

• chr1-152798041-C-G
• rs769606443
• NM_178352.3:c.247C>G

Variant summary

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

The NM_178352.3(LCE1D):​c.247C>G​(p.Arg83Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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. R83C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: LCE1D NM_178352.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10511637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE1D	NM_178352.3	c.247C>G	p.Arg83Gly	missense_variant	Exon 2 of 2	ENST00000326233.7	NP_848129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE1D	ENST00000326233.7	c.247C>G	p.Arg83Gly	missense_variant	Exon 2 of 2	5	NM_178352.3	ENSP00000316737.6

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ExAC AF: 0.00000889 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.4
DANN	Benign	0.33
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.0	M
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.057
Sift4G	Benign	0.14	T
Polyphen		0.019	B
Vest4		0.33
MutPred		0.17		Loss of MoRF binding (P = 0.0597);
MVP		0.18
MPC		0.38
ClinPred		0.99	D
GERP RS		-2.0
Varity_R		0.58
gMVP		0.044

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

Publications

LitVar

Other links and lift over

dbSNP: rs769606443; hg19: chr1-152770517;