8-70661863-G-C

Position:

• chr8-70661863-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016027.3(LACTB2):​c.157C>G​(p.Pro53Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.9e-7 (0 hom.)
• Consequence: LACTB2 NM_016027.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54

Genes affected

LACTB2 (HGNC:18512): (lactamase beta 2) Enables endoribonuclease activity; single-stranded RNA binding activity; and zinc ion binding activity. Involved in RNA phosphodiester bond hydrolysis, endonucleolytic. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

LACTB2-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB2	NM_016027.3	c.157C>G	p.Pro53Ala	missense_variant	2/7	ENST00000276590.5	NP_057111.1
LACTB2-AS1	NR_038881.1	n.2300G>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB2	ENST00000276590.5	c.157C>G	p.Pro53Ala	missense_variant	2/7	1	NM_016027.3	ENSP00000276590.4
LACTB2-AS1	ENST00000499227.6	n.2300G>C		non_coding_transcript_exon_variant	4/4	1
LACTB2	ENST00000522447.5	c.157C>G	p.Pro53Ala	missense_variant	2/8	2		ENSP00000428801.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458072 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725234

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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

Sep 03, 2024

The c.157C>G (p.P53A) alteration is located in exon 2 (coding exon 2) of the LACTB2 gene. This alteration results from a C to G substitution at nucleotide position 157, causing the proline (P) at amino acid position 53 to be replaced by an alanine (A). 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	0.083
BayesDel_addAF	Benign	0.0074	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;D
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.52
Sift	Benign	0.20	T;T
Sift4G	Benign	0.10	T;T
Polyphen		1.0	D;D
Vest4		0.58
MutPred		0.47		Loss of glycosylation at P53 (P = 0.1533);Loss of glycosylation at P53 (P = 0.1533);
MVP		0.88
MPC		0.029
ClinPred		0.89	D
GERP RS		3.8
Varity_R		0.48
gMVP		0.76

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: rs1020756367; hg19: chr8-71574098;