dbSNP rs771140387: LACTB2:p.His287Leu (chr8-70637867-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016027.3(LACTB2):c.860A>T(p.His287Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H287Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LACTB2
NM_016027.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.336

Publications

0 publications found

Variant links:

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 links:

LACTB2-AS1 (HGNC:27841): (LACTB2 antisense RNA 1)

LACTB2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05081448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LACTB2	NM_016027.3 link	c.860A>T	p.His287Leu	missense_variant	Exon 7 of 7	ENST00000276590.5	NP_057111.1	Q53H82A0A024R811
LACTB2-AS1	NR_038881.1 link	n.258-13946T>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LACTB2	ENST00000276590.5 link	c.860A>T	p.His287Leu	missense_variant	Exon 7 of 7	1	NM_016027.3	ENSP00000276590.4		Q53H82

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000908

AC:

AN:

220220

AF XY:

0.0000167

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000957

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1399762

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

695704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30756

American (AMR)

AF:

0.00

AC:

AN:

37346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24584

East Asian (EAS)

AF:

0.00

AC:

AN:

37456

South Asian (SAS)

AF:

0.00

AC:

AN:

74348

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1080302

Other (OTH)

AF:

0.00

AC:

AN:

57598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 28, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.860A>T (p.H287L) alteration is located in exon 7 (coding exon 7) of the LACTB2 gene. This alteration results from a A to T substitution at nucleotide position 860, causing the histidine (H) at amino acid position 287 to be replaced by a leucine (L). 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

0.088

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.42

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.7

L;L

PhyloP100

0.34

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.23

Sift

Benign

0.61

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0050

B;B

Vest4

0.18

MutPred

0.35

Gain of stability (P = 0.0114);Gain of stability (P = 0.0114);

MVP

0.52

MPC

0.031

ClinPred

0.057

GERP RS

2.4

Varity_R

0.21

gMVP

0.28

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over