16-25169578-A-G

Variant names:

• chr16-25169578-A-G
• rs277892
• NM_016309.3:c.792+365A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 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.792+365A>G		intron	N/A	NP_057393.2
	LCMT1	NM_001032391.2		c.627+365A>G		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.792+365A>G		intron	N/A	ENSP00000382021.3
	LCMT1	ENST00000380962.9	TSL:2	n.*649+365A>G		intron	N/A	ENSP00000370349.5
	LCMT1	ENST00000380966.8	TSL:2	c.627+365A>G		intron	N/A	ENSP00000370353.4

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

African (AFR) AF: 0.178 AC: 315 AN: 1772

American (AMR) AF: 0.329 AC: 973 AN: 2956

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 196 AN: 832

East Asian (EAS) AF: 0.330 AC: 813 AN: 2460

South Asian (SAS) AF: 0.276 AC: 877 AN: 3182

European-Finnish (FIN) AF: 0.181 AC: 172 AN: 948

Middle Eastern (MID) AF: 0.250 AC: 25 AN: 100

European-Non Finnish (NFE) AF: 0.209 AC: 3764 AN: 17980

Other (OTH) AF: 0.237 AC: 385 AN: 1624

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

African (AFR) AF: 0.195 AC: 8108 AN: 41484

American (AMR) AF: 0.316 AC: 4824 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1745 AN: 5162

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4814

European-Finnish (FIN) AF: 0.194 AC: 2050 AN: 10552

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14931 AN: 67972

Other (OTH) AF: 0.252 AC: 533 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.70
PhyloP100		0.57
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: rs277892; hg19: chr16-25180899;