Genetic Variant LACTB2:p.Lys283Arg (chr8-70637879-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is . The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016027.3(LACTB2):c.848A>G(p.Lys283Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 1,558,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

LACTB2
NM_016027.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

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

new If you want to explore the variant's impact on the transcript NM_016027.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016027.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACTB2	NM_016027.3	MANE Select	c.848A>G	p.Lys283Arg	missense	Exon 7 of 7	NP_057111.1	A0A024R811
	LACTB2-AS1	NR_038881.1		n.258-13934T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LACTB2	ENST00000276590.5	TSL:1 MANE Select	c.848A>G	p.Lys283Arg	missense	Exon 7 of 7	ENSP00000276590.4	Q53H82
LACTB2-AS1	ENST00000499227.6	TSL:1	n.258-13934T>C		intron	N/A
LACTB2	ENST00000522447.5	TSL:2	c.848A>G	p.Lys283Arg	missense	Exon 7 of 8	ENSP00000428801.1	Q53H82

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000224

AC:

AN:

223608

AF XY:

0.0000165

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000924

AC:

AN:

1406588

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

699086

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31026

American (AMR)

AF:

0.0000787

AC:

AN:

38116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24682

East Asian (EAS)

AF:

0.00

AC:

AN:

37668

South Asian (SAS)

AF:

0.00

AC:

AN:

75270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51946

Middle Eastern (MID)

AF:

0.000358

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.00000369

AC:

AN:

1084436

Other (OTH)

AF:

0.0000518

AC:

AN:

57860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.062

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.61

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.16

MetaSVM

Uncertain

-0.088

MutationAssessor

Benign

1.1

PhyloP100

3.4

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.97

REVEL

Uncertain

0.33

Sift

Benign

0.36

Sift4G

Benign

0.45

Varity_R

0.16

gMVP

0.11

Mutation Taster

=85/15

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over