15-63129587-A-T

Variant names:

• chr15-63129587-A-T
• rs1396651361
• NM_032857.5:c.1055A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

RPS27L (HGNC:18476): (ribosomal protein S27 like) This gene encodes a protein sharing 96% amino acid similarity with ribosomal protein S27, which suggests the encoded protein may be a component of the 40S ribosomal subunit. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.24018702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032857.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACTB	NM_032857.5	MANE Select	c.1055A>T	p.His352Leu	missense	Exon 5 of 6	NP_116246.2
	LACTB	NM_171846.4		c.1055A>T	p.His352Leu	missense	Exon 5 of 5	NP_741982.1	P83111-2
	LACTB	NM_001288585.2		c.*52A>T		3_prime_UTR	Exon 5 of 5	NP_001275514.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACTB	ENST00000261893.9	TSL:1 MANE Select	c.1055A>T	p.His352Leu	missense	Exon 5 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.1055A>T	p.His352Leu	missense	Exon 5 of 5	ENSP00000392956.2	P83111-2
	LACTB	ENST00000559782.1	TSL:2	n.229A>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.075
Sift	Benign	0.10	T
Sift4G	Uncertain	0.051	T
Polyphen		0.016	B
Vest4		0.51
MutPred		0.59		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

Other links and lift over

dbSNP: rs1396651361; hg19: chr15-63421786;