Variant chr1-152600987-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178434.3(LCE3C):c.256C>T(p.Arg86Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 948,488 control chromosomes in the GnomAD database, including 1,211 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R86H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.020 ( 565 hom., cov: 15)

Exomes 𝑓: 0.0023 ( 646 hom. )

Consequence

LCE3C
NM_178434.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.914

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021066368).

BP6

Variant 1-152600987-C-T is Benign according to our data. Variant chr1-152600987-C-T is described in ClinVar as [Benign]. Clinvar id is 712085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE3C	NM_178434.3 link	c.256C>T	p.Arg86Cys	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.256C>T	p.Arg86Cys	missense_variant	Exon 2 of 2		NM_178434.3	ENSP00000507204.1		Q5T5A8
LCE3C	ENST00000333881.3 link	c.256C>T	p.Arg86Cys	missense_variant	Exon 1 of 1	6		ENSP00000334644.3		Q5T5A8

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

1917

AN:

95554

Hom.:

562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00689

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00117

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000128

Gnomad OTH

AF:

0.0176

GnomAD3 exomes

AF:

0.00597

AC:

891

AN:

149336

Hom.:

287

AF XY:

0.00462

AC XY:

372

AN XY:

80480

show subpopulations

Gnomad AFR exome

AF:

0.0624

Gnomad AMR exome

AF:

0.00254

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000277

Gnomad OTH exome

AF:

0.00352

GnomAD4 exome

AF:

0.00232

AC:

1979

AN:

852836

Hom.:

646

Cov.:

AF XY:

0.00203

AC XY:

860

AN XY:

423780

show subpopulations

Gnomad4 AFR exome

AF:

0.0603

Gnomad4 AMR exome

AF:

0.00287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000503

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.0201

AC:

1925

AN:

95652

Hom.:

565

Cov.:

AF XY:

0.0204

AC XY:

938

AN XY:

46068

show subpopulations

Gnomad4 AFR

AF:

0.0565

Gnomad4 AMR

AF:

0.00676

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00117

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000128

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0125

Hom.:

ESP6500AA

AF:

0.0521

AC:

188

ESP6500EA

AF:

0.000941

AC:

ExAC

AF:

0.00677

AC:

540

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.00051

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.26

PROVEAN

Benign

REVEL

Benign

0.036

Sift

Benign

0.86

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.23

MVP

0.14

MPC

1.0

ClinPred

0.011

GERP RS

2.8

Varity_R

0.051

gMVP

0.046

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