rs8062337

chr16-25116120-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016309.3(LCMT1):c.113+4124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,214 control chromosomes in the GnomAD database, including 5,067 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5067 hom., cov: 32)
• Consequence: LCMT1 NM_016309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

Genes affected

LCMT1 (HGNC:17557): (leucine carboxyl methyltransferase 1) LCMT1 catalyzes the methylation of the carboxyl group of the C-terminal leucine residue (leu309) of the catalytic subunit of protein phosphatase-2A (PPP2CA; MIM 176915) (De Baere et al., 1999 [PubMed 10600115]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCMT1	NM_016309.3	c.113+4124G>A		intron_variant		ENST00000399069.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCMT1	ENST00000399069.8	c.113+4124G>A		intron_variant		1	NM_016309.3	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38908 AN: 152096 Hom.: 5061 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.278

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.256 AC: 38927 AN: 152214 Hom.: 5067 Cov.: 32 AF XY: 0.256 AC XY: 19058 AN XY: 74422

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.281

Alfa AF: 0.254 Hom.: 933

Bravo AF: 0.263

Asia WGS AF: 0.341 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.75
Dann	Benign	0.23

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

Other links and lift over

dbSNP: rs8062337; hg19: chr16-25127441;