1-152600987-C-T

Variant names:

• chr1-152600987-C-T
• rs73019253
• NM_178434.3:c.256C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 14/20 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.914
• Publications: 2 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 -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 VariationId 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.

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.256C>T	p.Arg86Cys	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.256C>T	p.Arg86Cys	missense	Exon 2 of 2	ENSP00000507204.1	Q5T5A8
	LCE3C	ENST00000333881.3	TSL:6	c.256C>T	p.Arg86Cys	missense	Exon 1 of 1	ENSP00000334644.3	Q5T5A8

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 1917 AN: 95554 Hom.: 562 Cov.: 15

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

GnomAD2 exomes AF: 0.00597 AC: 891 AN: 149336 AF XY: 0.00462

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 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.: 26 AF XY: 0.00203 AC XY: 860 AN XY: 423780

African (AFR) AF: 0.0603 AC: 1662 AN: 27548

American (AMR) AF: 0.00287 AC: 77 AN: 26790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15774

East Asian (EAS) AF: 0.00 AC: 0 AN: 25242

South Asian (SAS) AF: 0.000197 AC: 10 AN: 50850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30246

Middle Eastern (MID) AF: 0.00473 AC: 17 AN: 3596

European-Non Finnish (NFE) AF: 0.0000503 AC: 32 AN: 636466

Other (OTH) AF: 0.00498 AC: 181 AN: 36324

GnomAD4 genome AF: 0.0201 AC: 1925 AN: 95652 Hom.: 565 Cov.: 15 AF XY: 0.0204 AC XY: 938 AN XY: 46068

African (AFR) AF: 0.0565 AC: 1834 AN: 32480

American (AMR) AF: 0.00676 AC: 60 AN: 8876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2122

East Asian (EAS) AF: 0.00 AC: 0 AN: 2958

South Asian (SAS) AF: 0.00117 AC: 3 AN: 2562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5598

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

European-Non Finnish (NFE) AF: 0.000128 AC: 5 AN: 38948

Other (OTH) AF: 0.0175 AC: 23 AN: 1314

Alfa AF: 0.0132 Hom.: 49

ESP6500AA AF: 0.0521 AC: 188

ESP6500EA AF: 0.000941 AC: 5

ExAC AF: 0.00677 AC: 540

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.71
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.00051	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.94	T
PhyloP100		0.91
PrimateAI	Benign	0.26	T
PROVEAN	Benign	10	N
REVEL	Benign	0.036
Sift	Benign	0.86	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.23
MVP		0.14
MPC		1.0
ClinPred		0.011	T
GERP RS		2.8
PromoterAI		-0.0086	Neutral
Varity_R		0.051
gMVP		0.046
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73019253; hg19: chr1-152573463;