15-63127543-A-C

Position:

• chr15-63127543-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032857.5(LACTB):​c.806A>C​(p.Gln269Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

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:18476): (ribosomal protein S27 like) This gene encodes a protein sharing 96% amino acid similarity with ribosomal protein S27, which suggests the encoded protein may be a component of the 40S ribosomal subunit. [provided by RefSeq, Jul 2008]

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=0.08681059).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5	c.806A>C	p.Gln269Pro	missense_variant	4/6	ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.806A>C	p.Gln269Pro	missense_variant	4/5		NP_741982.1
LACTB	NM_001288585.2	c.806A>C	p.Gln269Pro	missense_variant	4/5		NP_001275514.1
LACTB	XM_047432128.1	c.806A>C	p.Gln269Pro	missense_variant	4/6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.806A>C	p.Gln269Pro	missense_variant	4/6	1	NM_032857.5	ENSP00000261893	P1
LACTB	ENST00000413507.3	c.806A>C	p.Gln269Pro	missense_variant	4/5	1		ENSP00000392956
LACTB	ENST00000557972.1	c.329A>C	p.Gln110Pro	missense_variant	3/3	2		ENSP00000454085
RPS27L	ENST00000559763.1	n.96-1523T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Mar 11, 2024

The c.806A>C (p.Q269P) alteration is located in exon 4 (coding exon 4) of the LACTB gene. This alteration results from a A to C substitution at nucleotide position 806, causing the glutamine (Q) at amino acid position 269 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	Benign	0.055
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.0094	T;.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.55	T;T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.
MutationTaster	Benign	0.51	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.059
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.26
MutPred		0.46		Gain of glycosylation at Q269 (P = 0.0306);Gain of glycosylation at Q269 (P = 0.0306);.;
MVP		0.58
MPC		0.41
ClinPred		0.31	T
GERP RS		3.7
Varity_R		0.12
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr15-63419742;