15-63121921-G-T

Variant names:

• chr15-63121921-G-T
• rs778350908
• NM_032857.5:c.50G>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.50G>T​(p.Gly17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000785 in 1,273,918 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. 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. G17A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662
• 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]

LOC107984798 (HGNC:):

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=0.21695304).

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.50G>T	p.Gly17Val	missense	Exon 1 of 6	NP_116246.2
	LACTB	NM_171846.4		c.50G>T	p.Gly17Val	missense	Exon 1 of 5	NP_741982.1	P83111-2
	LACTB	NM_001288585.2		c.50G>T	p.Gly17Val	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.50G>T	p.Gly17Val	missense	Exon 1 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.50G>T	p.Gly17Val	missense	Exon 1 of 5	ENSP00000392956.2	P83111-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.85e-7 AC: 1 AN: 1273918 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 627358

African (AFR) AF: 0.00 AC: 0 AN: 26476

American (AMR) AF: 0.00 AC: 0 AN: 22164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19624

East Asian (EAS) AF: 0.00 AC: 0 AN: 30324

South Asian (SAS) AF: 0.00 AC: 0 AN: 60722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4550

European-Non Finnish (NFE) AF: 9.75e-7 AC: 1 AN: 1026140

Other (OTH) AF: 0.00 AC: 0 AN: 52264

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.66
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.034
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.52	P
Vest4		0.14
MutPred		0.31		Loss of disorder (P = 0.0206)
MVP		0.69
MPC		0.45
ClinPred		0.15	T
GERP RS		2.2
PromoterAI		0.064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.098
gMVP		0.39
Mutation Taster		=89/11	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: rs778350908; hg19: chr15-63414120;