15-63122140-C-T

Variant names:

• chr15-63122140-C-T
• rs767923145
• NM_032857.5:c.269C>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.269C>T​(p.Pro90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000371 in 1,348,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676

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

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=0.06838575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LACTB	NM_032857.5	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 6	ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 5		NP_741982.1
LACTB	NM_001288585.2	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 5		NP_001275514.1
LACTB	XM_047432128.1	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 6	1	NM_032857.5	ENSP00000261893.4
LACTB	ENST00000413507.3	c.269C>T	p.Pro90Leu	missense_variant	Exon 1 of 5	1		ENSP00000392956.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000107 AC: 1 AN: 93482 Hom.: 0 AF XY: 0.0000188 AC XY: 1 AN XY: 53218

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000178

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000371 AC: 5 AN: 1348604 Hom.: 0 Cov.: 35 AF XY: 0.00000301 AC XY: 2 AN XY: 665438

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000316

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000282

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.4
DANN	Benign	0.89
DEOGEN2	Benign	0.0060	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.61	T;T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.65	N;N
REVEL	Benign	0.010
Sift	Benign	0.48	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.0050	B;.
Vest4		0.076
MutPred		0.23		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.25
MPC		0.34
ClinPred		0.048	T
GERP RS		-0.45
Varity_R		0.021
gMVP		0.42

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

LitVar

Other links and lift over

dbSNP: rs767923145; hg19: chr15-63414339;