16-25132453-G-C

Variant names:

• chr16-25132453-G-C
• rs751848262
• NM_016309.3:c.257G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016309.3(LCMT1):​c.257G>C​(p.Arg86Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R86Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LCMT1 NM_016309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2851985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCMT1	NM_016309.3	c.257G>C	p.Arg86Pro	missense_variant	Exon 3 of 11	ENST00000399069.8	NP_057393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCMT1	ENST00000399069.8	c.257G>C	p.Arg86Pro	missense_variant	Exon 3 of 11	1	NM_016309.3	ENSP00000382021.3
LCMT1	ENST00000380962.9	n.*114G>C		non_coding_transcript_exon_variant	Exon 4 of 12	2		ENSP00000370349.5
LCMT1	ENST00000380962.9	n.*114G>C		3_prime_UTR_variant	Exon 4 of 12	2		ENSP00000370349.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.;.
Eigen	Benign	-0.066
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M;.
PhyloP100		0.17
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D;D;.
Sift4G	Uncertain	0.033	D;D;D
Polyphen		0.57	P;P;.
Vest4		0.58
MVP		0.34
MPC		0.55
ClinPred		0.97	D
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.79
gMVP		0.79

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: rs751848262; hg19: chr16-25143774;