dbSNP rs761876414: LACTB2:p.Gly144Ser (chr8-70644227-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_016027.3(LACTB2):c.430G>A(p.Gly144Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,589,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

LACTB2
NM_016027.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

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 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.951

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.430G>A	p.Gly144Ser	missense	Exon 4 of 7	NP_057111.1	A0A024R811
	LACTB2-AS1	NR_038881.1		n.258-7586C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LACTB2	ENST00000276590.5	TSL:1 MANE Select	c.430G>A	p.Gly144Ser	missense	Exon 4 of 7	ENSP00000276590.4	Q53H82
LACTB2-AS1	ENST00000499227.6	TSL:1	n.258-7586C>T		intron	N/A
LACTB2	ENST00000522447.5	TSL:2	c.430G>A	p.Gly144Ser	missense	Exon 4 of 8	ENSP00000428801.1	Q53H82

Frequencies

GnomAD3 genomes

AF:

0.000205

AC:

AN:

150854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000704

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.0000212

AC:

AN:

236346

AF XY:

0.0000235

show subpopulations

Gnomad AFR exome

AF:

0.000188

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:

0.00

GnomAD4 exome

AF:

0.0000271

AC:

AN:

1438942

Hom.:

Cov.:

AF XY:

0.0000349

AC XY:

AN XY:

715320

show subpopulations

African (AFR)

AF:

0.000765

AC:

AN:

32698

American (AMR)

AF:

0.00

AC:

AN:

40876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25286

East Asian (EAS)

AF:

0.00

AC:

AN:

39498

South Asian (SAS)

AF:

0.0000855

AC:

AN:

81824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53064

Middle Eastern (MID)

AF:

0.000352

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100522

Other (OTH)

AF:

0.0000840

AC:

AN:

59490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.000205

AC:

AN:

150854

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

AN XY:

73708

show subpopulations

African (AFR)

AF:

0.000704

AC:

AN:

41220

American (AMR)

AF:

0.00

AC:

AN:

15102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67242

Other (OTH)

AF:

0.000481

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000230

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.0000247

AC:

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

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.1

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.95

MetaSVM

Uncertain

0.50

MutationAssessor

Pathogenic

5.0

PhyloP100

7.6

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.96

MVP

0.89

MPC

0.22

ClinPred

0.97

GERP RS

6.2

Varity_R

0.95

gMVP

0.97

Mutation Taster

=7/93

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over