Variant chr1-152600927-C-T 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.196C>T(p.Arg66Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 949,384 control chromosomes in the GnomAD database, including 7 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R66Q) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000022 ( 6 hom. )

Consequence

LCE3C
NM_178434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.07

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=0.14010462).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE3C	NM_178434.3 link	c.196C>T	p.Arg66Trp	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.196C>T	p.Arg66Trp	missense_variant	Exon 2 of 2		NM_178434.3	ENSP00000507204.1		Q5T5A8
LCE3C	ENST00000333881.3 link	c.196C>T	p.Arg66Trp	missense_variant	Exon 1 of 1	6		ENSP00000334644.3		Q5T5A8

Frequencies

GnomAD3 genomes

AF:

0.0000315

AC:

AN:

95364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000619

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000388

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000198

AC:

AN:

151384

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

81346

show subpopulations

Gnomad AFR exome

AF:

0.000225

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000222

AC:

AN:

854020

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

424492

show subpopulations

Gnomad4 AFR exome

AF:

0.000145

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000196

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000204

Gnomad4 OTH exome

AF:

0.0000275

GnomAD4 genome

AF:

0.0000315

AC:

AN:

95364

Hom.:

Cov.:

AF XY:

0.0000218

AC XY:

AN XY:

45888

show subpopulations

Gnomad4 AFR

AF:

0.0000619

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000388

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

May 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.196C>T (p.R66W) alteration is located in exon 1 (coding exon 1) of the LCE3C gene. This alteration results from a C to T substitution at nucleotide position 196, causing the arginine (R) at amino acid position 66 to be replaced by a tryptophan (W). 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

0.10

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.050

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.55

M_CAP

Benign

0.0032

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-7.3

REVEL

Benign

0.076

Sift

Uncertain

0.0010

Sift4G

Benign

0.10

Polyphen

0.98

Vest4

0.28

MutPred

0.22

Gain of catalytic residue at R66 (P = 0.0182);

MVP

0.32

MPC

0.78

ClinPred

0.22

GERP RS

-0.028

Varity_R

0.24

gMVP

0.058

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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