dbSNP rs1303186459: LCMT1:p.Ser15Tyr (chr16-25111927-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016309.3(LCMT1):c.44C>A(p.Ser15Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LCMT1
NM_016309.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Publications

0 publications found

Variant links:

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]

LCMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.081637174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCMT1	NM_016309.3 link	c.44C>A	p.Ser15Tyr	missense_variant	Exon 1 of 11	ENST00000399069.8	NP_057393.2	Q9UIC8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCMT1	ENST00000399069.8 link	c.44C>A	p.Ser15Tyr	missense_variant	Exon 1 of 11	1	NM_016309.3	ENSP00000382021.3		Q9UIC8-1
LCMT1	ENST00000380962.9 link	n.44C>A		non_coding_transcript_exon_variant	Exon 1 of 12	2		ENSP00000370349.5		H7BYF0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248160

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461246

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111708

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.44C>A (p.S15Y) alteration is located in exon 1 (coding exon 1) of the LCMT1 gene. This alteration results from a C to A substitution at nucleotide position 44, causing the serine (S) at amino acid position 15 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.18

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PhyloP100

1.8

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.047

B;B

Vest4

0.27

MutPred

0.25

Loss of disorder (P = 0.0162);Loss of disorder (P = 0.0162);

MVP

0.34

MPC

0.53

ClinPred

0.11

GERP RS

-1.3

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.21

gMVP

0.42

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over