15-43328899-G-A

Position:

• chr15-43328899-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014793.5(LCMT2):​c.1591C>T​(p.Pro531Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LCMT2 NM_014793.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71

Genes affected

LCMT2 (HGNC:17558): (leucine carboxyl methyltransferase 2) The protein encoded by this intronless gene belongs to the highly variable methyltransferase superfamily. This gene is the inferred homolog of the Saccharomyces cerevisiae carboxymethyltransferase gene PPM2 that is essential for the synthesis of the hypermodified guanosine Wybutosine (yW). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCMT2	NM_014793.5	c.1591C>T	p.Pro531Ser	missense_variant	1/1	ENST00000305641.7	NP_055608.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCMT2	ENST00000305641.7	c.1591C>T	p.Pro531Ser	missense_variant	1/1	6	NM_014793.5	ENSP00000307214.5
LCMT2	ENST00000567039.1	c.*719C>T		3_prime_UTR_variant	2/2	2		ENSP00000457403.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.1591C>T (p.P531S) alteration is located in exon 1 (coding exon 1) of the LCMT2 gene. This alteration results from a C to T substitution at nucleotide position 1591, causing the proline (P) at amino acid position 531 to be replaced by a serine (S). 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	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.033	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.34		Gain of glycosylation at P531 (P = 0.0254);
MVP		0.72
MPC		0.65
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-43621097;