Variant 1-152797997-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178352.3(LCE1D):c.203G>A(p.Gly68Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,440,226 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 1 hom., cov: 21)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

LCE1D
NM_178352.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.948

Variant links:

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]

LCE1D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14820057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCE1D	NM_178352.3 linkuse as main transcript	c.203G>A	p.Gly68Asp	missense_variant	2/2	ENST00000326233.7	NP_848129.1	Q5T752

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCE1D	ENST00000326233.7 linkuse as main transcript	c.203G>A	p.Gly68Asp	missense_variant	2/2	5	NM_178352.3	ENSP00000316737.6		Q5T752

Frequencies

GnomAD3 genomes

AF:

0.0000148

AC:

AN:

134994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000529

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000153

AC:

AN:

1305232

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

650172

show subpopulations

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:

0.00000205

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000148

AC:

AN:

134994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

65914

show subpopulations

Gnomad4 AFR

AF:

0.0000529

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.203G>A (p.G68D) 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 203, causing the glycine (G) at amino acid position 68 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

0.19

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.25

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.21

M_CAP

Benign

0.0059

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.98

MutationAssessor

Pathogenic

2.9

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.031

Sift4G

Uncertain

0.034

Polyphen

0.0010

Vest4

0.28

MVP

0.33

MPC

0.38

ClinPred

0.24

GERP RS

2.1

Varity_R

0.53

gMVP

0.014

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over