rs139364914

Variant names:

• chr1-152600994-A-G
• rs139364914
• NM_178434.3:c.263A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_178434.3(LCE3C):​c.263A>G​(p.His88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00073 in 948,262 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (20 hom., cov: 15)
  • Exomes 𝑓: 0.00075 (256 hom.)
• Consequence: LCE3C NM_178434.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.173
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03285107).
• BS2: High Homozygotes in GnomAd4 at 20 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.263A>G	p.His88Arg	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.263A>G	p.His88Arg	missense	Exon 2 of 2	ENSP00000507204.1	Q5T5A8
	LCE3C	ENST00000333881.3	TSL:6	c.263A>G	p.His88Arg	missense	Exon 1 of 1	ENSP00000334644.3	Q5T5A8

Frequencies

GnomAD3 genomes AF: 0.000512 AC: 49 AN: 95652 Hom.: 20 Cov.: 15

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000339

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: 0.000949

Gnomad OTH AF: 0.00381

GnomAD2 exomes AF: 0.000369 AC: 55 AN: 149186 AF XY: 0.000386

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000784

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000754 AC: 643 AN: 852508 Hom.: 256 Cov.: 26 AF XY: 0.000774 AC XY: 328 AN XY: 423538

African (AFR) AF: 0.000218 AC: 6 AN: 27546

American (AMR) AF: 0.00 AC: 0 AN: 26772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15758

East Asian (EAS) AF: 0.00 AC: 0 AN: 25234

South Asian (SAS) AF: 0.00 AC: 0 AN: 50816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3592

European-Non Finnish (NFE) AF: 0.000970 AC: 617 AN: 636238

Other (OTH) AF: 0.000551 AC: 20 AN: 36320

GnomAD4 genome AF: 0.000512 AC: 49 AN: 95754 Hom.: 20 Cov.: 15 AF XY: 0.000521 AC XY: 24 AN XY: 46106

African (AFR) AF: 0.000123 AC: 4 AN: 32538

American (AMR) AF: 0.000338 AC: 3 AN: 8870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2120

East Asian (EAS) AF: 0.00 AC: 0 AN: 2970

South Asian (SAS) AF: 0.00 AC: 0 AN: 2562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 180

European-Non Finnish (NFE) AF: 0.000949 AC: 37 AN: 38978

Other (OTH) AF: 0.00378 AC: 5 AN: 1324

Alfa AF: 0.000157 Hom.: 2

ESP6500AA AF: 0.000277 AC: 1

ESP6500EA AF: 0.000374 AC: 2

ExAC AF: 0.000264 AC: 21

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.2
DANN	Benign	0.43
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.17
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.072
Sift	Benign	0.030	D
Sift4G	Benign	0.31	T
Polyphen		0.22	B
Vest4		0.15
MVP		0.12
MPC		0.91
ClinPred		0.041	T
GERP RS		-2.8
PromoterAI		-0.0060	Neutral
Varity_R		0.16
gMVP		0.029
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs139364914; hg19: chr1-152573470;