Variant 1-152600944-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_178434.3(LCE3C):c.213C>A(p.Asn71Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 949,928 control chromosomes in the GnomAD database, including 439 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 169 hom., cov: 15)

Exomes 𝑓: 0.00098 ( 270 hom. )

Consequence

LCE3C
NM_178434.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.58

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=0.003818214).

BP6

Variant 1-152600944-C-A is Benign according to our data. Variant chr1-152600944-C-A is described in ClinVar as [Benign]. Clinvar id is 790491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00634 (607/95802) while in subpopulation AFR AF= 0.0175 (569/32516). AF 95% confidence interval is 0.0163. There are 169 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 15. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 169 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE3C	NM_178434.3 link	c.213C>A	p.Asn71Lys	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.213C>A	p.Asn71Lys	missense_variant	Exon 2 of 2		NM_178434.3	ENSP00000507204.1		Q5T5A8
LCE3C	ENST00000333881.3 link	c.213C>A	p.Asn71Lys	missense_variant	Exon 1 of 1	6		ENSP00000334644.3		Q5T5A8

Frequencies

GnomAD3 genomes

AF:

0.00635

AC:

608

AN:

95698

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00258

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:

0.000154

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00188

AC:

284

AN:

151170

Hom.:

AF XY:

0.00153

AC XY:

124

AN XY:

81276

show subpopulations

Gnomad AFR exome

AF:

0.0162

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.000325

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000348

Gnomad OTH exome

AF:

0.00161

GnomAD4 exome

AF:

0.000978

AC:

835

AN:

854126

Hom.:

270

Cov.:

AF XY:

0.000912

AC XY:

387

AN XY:

424554

show subpopulations

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.000126

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00634

AC:

607

AN:

95802

Hom.:

169

Cov.:

AF XY:

0.00616

AC XY:

284

AN XY:

46138

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.00247

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000154

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00392

Hom.:

ESP6500AA

AF:

0.0146

AC:

ESP6500EA

AF:

0.000370

AC:

ExAC

AF:

0.00197

AC:

159

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

- -

May 24, 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

0.22

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

DANN

Benign

0.26

DEOGEN2

Benign

0.017

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.90

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.031

Sift

Uncertain

0.010

Sift4G

Benign

0.074

Polyphen

0.058

Vest4

0.14

MutPred

0.17

Gain of catalytic residue at N71 (P = 0.0159);

MVP

0.11

MPC

0.86

ClinPred

0.018

GERP RS

0.84

Varity_R

0.17

gMVP

0.021

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