16-25151183-T-C

Position:

• chr16-25151183-T-C

Variant summary

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

The NM_016309.3(LCMT1):​c.405-371T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,076 control chromosomes in the GnomAD database, including 34,862 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 0.67 (34862 hom., cov: 32)
• Consequence: LCMT1 NM_016309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCMT1	NM_016309.3	c.405-371T>C		intron_variant		ENST00000399069.8	NP_057393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCMT1	ENST00000399069.8	c.405-371T>C		intron_variant		1	NM_016309.3	ENSP00000382021	P1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102288 AN: 151958 Hom.: 34865 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.673 AC: 102308 AN: 152076 Hom.: 34862 Cov.: 32 AF XY: 0.670 AC XY: 49839 AN XY: 74346

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.657

Alfa AF: 0.720 Hom.: 17798

Bravo AF: 0.657

Asia WGS AF: 0.597 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.58

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: rs277886; hg19: chr16-25162504;