15-63122148-C-T

Variant names:

• chr15-63122148-C-T
• rs1320187078
• NM_032857.5:c.277C>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.277C>T​(p.Pro93Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,358,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. P93T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• 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]

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=0.25430858).

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.277C>T	p.Pro93Ser	missense	Exon 1 of 6	NP_116246.2
	LACTB	NM_171846.4		c.277C>T	p.Pro93Ser	missense	Exon 1 of 5	NP_741982.1	P83111-2
	LACTB	NM_001288585.2		c.277C>T	p.Pro93Ser	missense	Exon 1 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.277C>T	p.Pro93Ser	missense	Exon 1 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.277C>T	p.Pro93Ser	missense	Exon 1 of 5	ENSP00000392956.2	P83111-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000294 AC: 4 AN: 1358696 Hom.: 0 Cov.: 35 AF XY: 0.00000298 AC XY: 2 AN XY: 670674

African (AFR) AF: 0.00 AC: 0 AN: 28542

American (AMR) AF: 0.00 AC: 0 AN: 32278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23908

East Asian (EAS) AF: 0.0000610 AC: 2 AN: 32794

South Asian (SAS) AF: 0.00 AC: 0 AN: 77602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069474

Other (OTH) AF: 0.0000353 AC: 2 AN: 56628

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.72	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.20
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.048
Sift	Benign	0.046	D
Sift4G	Benign	0.56	T
Polyphen		0.92	P
Vest4		0.071
MutPred		0.19		Gain of phosphorylation at P93 (P = 0.0478)
MVP		0.50
MPC		0.35
ClinPred		0.21	T
GERP RS		3.3
PromoterAI		0.0020	Neutral
Varity_R		0.058
gMVP		0.43
Mutation Taster		=91/9	polymorphism

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: rs1320187078; hg19: chr15-63414347;