Variant 1-152600975-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_178434.3(LCE3C):c.244G>A(p.Gly82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 948,996 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000031 ( 1 hom., cov: 16)

Exomes 𝑓: 0.000011 ( 3 hom. )

Consequence

LCE3C
NM_178434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

LCE3C (HGNC:16612): (late cornified envelope 3C) Involved in defense response to Gram-negative bacterium; defense response to Gram-positive bacterium; and killing of cells of other organism. [provided by Alliance of Genome Resources, Apr 2022]

LCE3C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1539242).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE3C	NM_178434.3 link	c.244G>A	p.Gly82Arg	missense_variant	Exon 2 of 2	ENST00000684028.1	NP_848521.1	Q5T5A8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE3C	ENST00000684028.1 link	c.244G>A	p.Gly82Arg	missense_variant	Exon 2 of 2		NM_178434.3	ENSP00000507204.1		Q5T5A8
LCE3C	ENST00000333881.3 link	c.244G>A	p.Gly82Arg	missense_variant	Exon 1 of 1	6		ENSP00000334644.3		Q5T5A8

Frequencies

GnomAD3 genomes

AF:

0.0000313

AC:

AN:

95758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000615

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:

0.0000257

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000105

AC:

AN:

853238

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

424024

show subpopulations

Gnomad4 AFR exome

AF:

0.000109

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000393

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000628

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000313

AC:

AN:

95758

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

46062

show subpopulations

Gnomad4 AFR

AF:

0.0000615

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:

0.0000257

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

Apr 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.244G>A (p.G82R) alteration is located in exon 1 (coding exon 1) of the LCE3C gene. This alteration results from a G to A substitution at nucleotide position 244, causing the glycine (G) at amino acid position 82 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.45

DEOGEN2

Benign

0.016

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.34

M_CAP

Benign

0.0027

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.086

Sift

Benign

0.30

Sift4G

Uncertain

0.031

Polyphen

0.42

Vest4

0.32

MutPred

0.24

Gain of MoRF binding (P = 0.002);

MVP

0.24

MPC

0.89

ClinPred

0.16

GERP RS

3.1

Varity_R

0.12

gMVP

0.025

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