chr1-152798137-T-C

Variant names:

• chr1-152798137-T-C
• NM_178352.3:c.343T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_178352.3(LCE1D):​c.343T>C​(p.Ter115Argext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000806 in 1,241,098 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: LCE1D NM_178352.3 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830

Genes affected

LCE1D (HGNC:29465): (late cornified envelope 1D) Enables identical protein binding activity. Involved in cognition. Acts upstream of or within cellular response to calcium ion. Located in cornified envelope and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_178352.3 Downstream stopcodon found after 138 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE1D	NM_178352.3	c.343T>C	p.Ter115Argext*?	stop_lost	Exon 2 of 2	ENST00000326233.7	NP_848129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE1D	ENST00000326233.7	c.343T>C	p.Ter115Argext*?	stop_lost	Exon 2 of 2	5	NM_178352.3	ENSP00000316737.6

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 8.06e-7 AC: 1 AN: 1241098 Hom.: 0 Cov.: 30 AF XY: 0.00000163 AC XY: 1 AN XY: 612934

Gnomad4 AFR exome AF: 0.0000337

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	14
DANN	Benign	0.82
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.69	D
Vest4		0.0070
GERP RS		2.4

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-152770613;