chr16-25169578-A-G

Position:

• chr16-25169578-A-G

Variant summary

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

The NM_016309.3(LCMT1):​c.792+365A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 183,906 control chromosomes in the GnomAD database, including 5,085 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 0.23 (4061 hom., cov: 32)
  • Exomes 𝑓: 0.24 (1024 hom.)
• Consequence: LCMT1 NM_016309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575

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]

LCMT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCMT1	NM_016309.3	c.792+365A>G		intron_variant		ENST00000399069.8	NP_057393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCMT1	ENST00000399069.8	c.792+365A>G		intron_variant		1	NM_016309.3	ENSP00000382021.3
LCMT1	ENST00000380962.9	n.*649+365A>G		intron_variant		2		ENSP00000370349.5

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34616 AN: 151934 Hom.: 4049 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.236 AC: 7520 AN: 31854 Hom.: 1024 Cov.: 0 AF XY: 0.243 AC XY: 4042 AN XY: 16662

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.228 AC: 34647 AN: 152052 Hom.: 4061 Cov.: 32 AF XY: 0.230 AC XY: 17087 AN XY: 74316

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.252

Alfa AF: 0.210 Hom.: 424

Bravo AF: 0.236

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.70

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: rs277892; hg19: chr16-25180899;