chr1-152579699-C-G

Variant names:

• chr1-152579699-C-G
• rs746626130
• NM_032563.2:c.238G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032563.2(LCE3D):​c.238G>C​(p.Gly80Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LCE3D NM_032563.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 1 publications found

Genes affected

LCE3D (HGNC:16615): (late cornified envelope 3D) Predicted to be involved in keratinization. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38676214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE3D	NM_032563.2	c.238G>C	p.Gly80Arg	missense_variant	Exon 2 of 2	ENST00000368787.4	NP_115952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE3D	ENST00000368787.4	c.238G>C	p.Gly80Arg	missense_variant	Exon 2 of 2	1	NM_032563.2	ENSP00000357776.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461658 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727154

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.5
DANN	Benign	0.72
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.1
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.032
Sift	Benign	0.17	T
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.22		Gain of MoRF binding (P = 0.0115);
MVP		0.35
MPC		0.013
ClinPred		0.38	T
GERP RS		2.7
Varity_R		0.16
gMVP		0.022
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs746626130; hg19: chr1-152552175;