chr1-152797997-G-C

Variant names:

• chr1-152797997-G-C
• NM_178352.3:c.203G>C

Variant summary

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

The NM_178352.3(LCE1D):​c.203G>C​(p.Gly68Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,305,232 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. 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. G68D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: LCE1D NM_178352.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948

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=0.1285218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE1D	NM_178352.3	c.203G>C	p.Gly68Ala	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.203G>C	p.Gly68Ala	missense_variant	Exon 2 of 2	5	NM_178352.3	ENSP00000316737.6

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 7.66e-7 AC: 1 AN: 1305232 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 650172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	2.9	M
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.033
Sift4G	Benign	0.068	T
Polyphen		0.073	B
Vest4		0.28
MutPred		0.094		Gain of MoRF binding (P = 0.1166);
MVP		0.31
MPC		0.32
ClinPred		0.28	T
GERP RS		2.1
Varity_R		0.55
gMVP		0.018

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-152770473;