Genetic Variant NM_178434.3:c.213C>A (chr1-152600944-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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. 13/20 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

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 15. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 169 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178434.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE3C	NM_178434.3	MANE Select	c.213C>A	p.Asn71Lys	missense	Exon 2 of 2	NP_848521.1	Q5T5A8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE3C	ENST00000684028.1	MANE Select	c.213C>A	p.Asn71Lys	missense	Exon 2 of 2	ENSP00000507204.1	Q5T5A8
	LCE3C	ENST00000333881.3	TSL:6	c.213C>A	p.Asn71Lys	missense	Exon 1 of 1	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

GnomAD2 exomes

AF:

0.00188

AC:

284

AN:

151170

AF XY:

0.00153

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 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

African (AFR)

AF:

0.0203

AC:

561

AN:

27576

American (AMR)

AF:

0.00168

AC:

AN:

26848

Ashkenazi Jewish (ASJ)

AF:

0.000126

AC:

AN:

15862

East Asian (EAS)

AF:

0.00

AC:

AN:

25248

South Asian (SAS)

AF:

0.00

AC:

AN:

50946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30338

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

3662

European-Non Finnish (NFE)

AF:

0.000210

AC:

134

AN:

637252

Other (OTH)

AF:

0.00217

AC:

AN:

36394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00634

AC:

607

AN:

95802

Hom.:

169

Cov.:

AF XY:

0.00616

AC XY:

284

AN XY:

46138

show subpopulations

African (AFR)

AF:

0.0175

AC:

569

AN:

32516

American (AMR)

AF:

0.00247

AC:

AN:

8918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2092

East Asian (EAS)

AF:

0.00

AC:

AN:

2976

South Asian (SAS)

AF:

0.00

AC:

AN:

2600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

182

European-Non Finnish (NFE)

AF:

0.000154

AC:

AN:

38976

Other (OTH)

AF:

0.00758

AC:

AN:

1320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00392

Hom.:

ESP6500AA

AF:

0.0146

AC:

ESP6500EA

AF:

0.000370

AC:

ExAC

AF:

0.00197

AC:

159

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

(source)

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

PhyloP100

-1.6

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

PromoterAI

0.0077

Neutral

(source)

Varity_R

0.17

gMVP

0.021

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over