rs277898

Variant names:

• chr16-25160489-G-A
• rs277898
• NM_016309.3:c.467-613G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016309.3(LCMT1):​c.467-613G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,056 control chromosomes in the GnomAD database, including 8,659 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 0.31 (8659 hom., cov: 33)
• Consequence: LCMT1 NM_016309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCMT1	NM_016309.3	c.467-613G>A		intron_variant	Intron 5 of 10	ENST00000399069.8	NP_057393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCMT1	ENST00000399069.8	c.467-613G>A		intron_variant	Intron 5 of 10	1	NM_016309.3	ENSP00000382021.3
LCMT1	ENST00000380962.9	n.*324-613G>A		intron_variant	Intron 6 of 11	2		ENSP00000370349.5

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47035 AN: 151938 Hom.: 8665 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.309 AC: 47024 AN: 152056 Hom.: 8659 Cov.: 33 AF XY: 0.312 AC XY: 23175 AN XY: 74322

African (AFR) AF: 0.104 AC: 4321 AN: 41484

American (AMR) AF: 0.370 AC: 5654 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1417 AN: 3470

East Asian (EAS) AF: 0.502 AC: 2595 AN: 5170

South Asian (SAS) AF: 0.357 AC: 1721 AN: 4822

European-Finnish (FIN) AF: 0.356 AC: 3758 AN: 10546

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26440 AN: 67970

Other (OTH) AF: 0.315 AC: 666 AN: 2114

Alfa AF: 0.349 Hom.: 3932

Bravo AF: 0.303

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.67
DANN	Benign	0.64
PhyloP100		0.049
Mutation Taster		=100/0	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: rs277898; hg19: chr16-25171810;