15-63127003-A-C

Position:

• chr15-63127003-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032857.5(LACTB):​c.569A>C​(p.Gln190Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 9.08

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5	c.569A>C	p.Gln190Pro	missense_variant	3/6	ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.569A>C	p.Gln190Pro	missense_variant	3/5		NP_741982.1
LACTB	NM_001288585.2	c.569A>C	p.Gln190Pro	missense_variant	3/5		NP_001275514.1
LACTB	XM_047432128.1	c.569A>C	p.Gln190Pro	missense_variant	3/6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.569A>C	p.Gln190Pro	missense_variant	3/6	1	NM_032857.5	ENSP00000261893.4
LACTB	ENST00000413507.3	c.569A>C	p.Gln190Pro	missense_variant	3/5	1		ENSP00000392956.2
LACTB	ENST00000557972.1	c.92A>C	p.Gln31Pro	missense_variant	2/3	2		ENSP00000454085.1
RPS27L	ENST00000559763.1	n.96-983T>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.569A>C (p.Q190P) alteration is located in exon 3 (coding exon 3) of the LACTB gene. This alteration results from a A to C substitution at nucleotide position 569, causing the glutamine (Q) at amino acid position 190 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.5	L;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.9	D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.86
MutPred		0.68		Loss of catalytic residue at Q190 (P = 0.0786);Loss of catalytic residue at Q190 (P = 0.0786);.;
MVP		0.76
MPC		1.2
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.87
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-63419202;