chr16-25151183-T-C

Variant names:

• chr16-25151183-T-C
• rs277886
• NM_016309.3:c.405-371T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016309.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCMT1	NM_016309.3	MANE Select	c.405-371T>C		intron	N/A	NP_057393.2
	LCMT1	NM_001032391.2		c.404+10936T>C		intron	N/A	NP_001027563.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCMT1	ENST00000399069.8	TSL:1 MANE Select	c.405-371T>C		intron	N/A	ENSP00000382021.3
	LCMT1	ENST00000380962.9	TSL:2	n.*262-371T>C		intron	N/A	ENSP00000370349.5
	LCMT1	ENST00000380966.8	TSL:2	c.404+10936T>C		intron	N/A	ENSP00000370353.4

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

African (AFR) AF: 0.575 AC: 23824 AN: 41458

American (AMR) AF: 0.623 AC: 9511 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2464 AN: 3472

East Asian (EAS) AF: 0.527 AC: 2729 AN: 5174

South Asian (SAS) AF: 0.700 AC: 3372 AN: 4818

European-Finnish (FIN) AF: 0.736 AC: 7776 AN: 10572

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50304 AN: 67994

Other (OTH) AF: 0.657 AC: 1388 AN: 2112

Alfa AF: 0.719 Hom.: 19987

Bravo AF: 0.657

Asia WGS AF: 0.597 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.58
PhyloP100		0.46
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: rs277886; hg19: chr16-25162504;