15-63129587-A-T

Position:

• chr15-63129587-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032857.5(LACTB):​c.1055A>T​(p.His352Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

Genes affected

LACTB (HGNC:16468): (lactamase beta) This gene encodes a mitochondrially-localized protein that has sequence similarity to prokaryotic beta-lactamases. Many of the residues responsible for beta-lactamase activity are not conserved in this protein, suggesting it may have a different enzymatic function. Increased expression of the related mouse gene was found to be associated with obesity. Alternative splicing results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Dec 2013]

LACTB (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24018702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5	c.1055A>T	p.His352Leu	missense_variant	5/6	ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.1055A>T	p.His352Leu	missense_variant	5/5		NP_741982.1
LACTB	XM_047432128.1	c.1055A>T	p.His352Leu	missense_variant	5/6		XP_047288084.1
LACTB	NM_001288585.2	c.*52A>T		3_prime_UTR_variant	5/5		NP_001275514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.1055A>T	p.His352Leu	missense_variant	5/6	1	NM_032857.5	ENSP00000261893.4
LACTB	ENST00000413507.3	c.1055A>T	p.His352Leu	missense_variant	5/5	1		ENSP00000392956.2
LACTB	ENST00000559782.1	n.229A>T		non_coding_transcript_exon_variant	1/2	2
RPS27L	ENST00000559763.1	n.96-3567T>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jan 31, 2024

The c.1055A>T (p.H352L) alteration is located in exon 5 (coding exon 5) of the LACTB gene. This alteration results from a A to T substitution at nucleotide position 1055, causing the histidine (H) at amino acid position 352 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-0.062
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.075
Sift	Benign	0.10	T;T
Sift4G	Uncertain	0.051	T;D
Polyphen		0.016	B;.
Vest4		0.51
MutPred		0.59		Loss of methylation at K349 (P = 0.0603);Loss of methylation at K349 (P = 0.0603);
MVP		0.65
MPC		0.43
ClinPred		0.53	D
GERP RS		5.8
Varity_R		0.20
gMVP		0.59

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: chr15-63421786;