NM_032857.5:c.206C>T

Variant names:

• chr15-63122077-C-T
• NM_032857.5:c.206C>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.206C>T​(p.Pro69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,295,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000015 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.987
• 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=0.16364422).

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.206C>T	p.Pro69Leu	missense	Exon 1 of 6	NP_116246.2
	LACTB	NM_171846.4		c.206C>T	p.Pro69Leu	missense	Exon 1 of 5	NP_741982.1	P83111-2
	LACTB	NM_001288585.2		c.206C>T	p.Pro69Leu	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.206C>T	p.Pro69Leu	missense	Exon 1 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.206C>T	p.Pro69Leu	missense	Exon 1 of 5	ENSP00000392956.2	P83111-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1295788 Hom.: 0 Cov.: 35 AF XY: 0.00000157 AC XY: 1 AN XY: 636368

African (AFR) AF: 0.00 AC: 0 AN: 25926

American (AMR) AF: 0.00 AC: 0 AN: 22194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21068

East Asian (EAS) AF: 0.00 AC: 0 AN: 28246

South Asian (SAS) AF: 0.00 AC: 0 AN: 67674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3796

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1041548

Other (OTH) AF: 0.00 AC: 0 AN: 53754

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	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.99
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.047
Sift	Benign	0.48	T
Sift4G	Benign	0.38	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.25		Loss of glycosylation at P69 (P = 0.0204)
MVP		0.37
MPC		0.34
ClinPred		0.090	T
GERP RS		2.4
PromoterAI		-0.021	Neutral
Varity_R		0.062
gMVP		0.26
Mutation Taster		=86/14	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

hg19: chr15-63414276;