NM_016027.3:c.256A>G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016027.3(LACTB2):c.256A>G(p.Ile86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,460,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. I86T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

LACTB2
NM_016027.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15689424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LACTB2	NM_016027.3 link	c.256A>G	p.Ile86Val	missense_variant	Exon 2 of 7	ENST00000276590.5	NP_057111.1	Q53H82A0A024R811
LACTB2-AS1	NR_038881.1 link	n.2201T>C		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LACTB2	ENST00000276590.5 link	c.256A>G	p.Ile86Val	missense_variant	Exon 2 of 7	1	NM_016027.3	ENSP00000276590.4	Q53H82
LACTB2-AS1	ENST00000499227.6 link	n.2201T>C		non_coding_transcript_exon_variant	Exon 4 of 4	1
LACTB2	ENST00000522447.5 link	c.256A>G	p.Ile86Val	missense_variant	Exon 2 of 8	2		ENSP00000428801.1	Q53H82

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000400

AC:

AN:

249984

AF XY:

0.0000148

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:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1460452

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44332

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.000151

AC:

AN:

85836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111688

Other (OTH)

AF:

0.0000829

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 25, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.256A>G (p.I86V) alteration is located in exon 2 (coding exon 2) of the LACTB2 gene. This alteration results from a A to G substitution at nucleotide position 256, causing the isoleucine (I) at amino acid position 86 to be replaced by a valine (V). 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

0.084

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-0.38

N;N

PhyloP100

3.1

PrimateAI

Benign

0.42

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.28

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.12

B;B

Vest4

0.21

MutPred

0.69

Gain of disorder (P = 0.158);Gain of disorder (P = 0.158);

MVP

0.74

MPC

0.026

ClinPred

0.11

GERP RS

5.8

Varity_R

0.22

gMVP

0.63

Mutation Taster

=74/26

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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NM_016027.3:c.256A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over