8-70657873-T-C

Variant summary

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

The NM_016027.3(LACTB2):​c.296A>G​(p.Tyr99Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,593,414 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LACTB2
NM_016027.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LACTB2NM_016027.3 linkc.296A>G p.Tyr99Cys missense_variant Exon 3 of 7 ENST00000276590.5 NP_057111.1 Q53H82A0A024R811
LACTB2-AS1NR_038881.1 linkn.582-2272T>C intron_variant Intron 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LACTB2ENST00000276590.5 linkc.296A>G p.Tyr99Cys missense_variant Exon 3 of 7 1 NM_016027.3 ENSP00000276590.4 Q53H82
LACTB2-AS1ENST00000499227.6 linkn.582-2272T>C intron_variant Intron 3 of 3 1
LACTB2ENST00000522447.5 linkc.296A>G p.Tyr99Cys missense_variant Exon 3 of 8 2 ENSP00000428801.1 Q53H82

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152200
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000458
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000321
AC:
8
AN:
249316
AF XY:
0.0000297
show subpopulations
Gnomad AFR exome
AF:
0.000432
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:
0.000166
GnomAD4 exome
AF:
0.0000160
AC:
23
AN:
1441096
Hom.:
0
Cov.:
26
AF XY:
0.0000167
AC XY:
12
AN XY:
718246
show subpopulations
African (AFR)
AF:
0.000425
AC:
14
AN:
32928
American (AMR)
AF:
0.00
AC:
0
AN:
44320
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25926
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39490
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85504
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53188
Middle Eastern (MID)
AF:
0.000175
AC:
1
AN:
5710
European-Non Finnish (NFE)
AF:
9.14e-7
AC:
1
AN:
1094338
Other (OTH)
AF:
0.000117
AC:
7
AN:
59692
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.453
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000125
AC:
19
AN:
152318
Hom.:
0
Cov.:
31
AF XY:
0.0000940
AC XY:
7
AN XY:
74482
show subpopulations
African (AFR)
AF:
0.000457
AC:
19
AN:
41570
American (AMR)
AF:
0.00
AC:
0
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68028
Other (OTH)
AF:
0.00
AC:
0
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.528
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000142
Hom.:
0
Bravo
AF:
0.000110
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 04, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.296A>G (p.Y99C) alteration is located in exon 3 (coding exon 3) of the LACTB2 gene. This alteration results from a A to G substitution at nucleotide position 296, causing the tyrosine (Y) at amino acid position 99 to be replaced by a cysteine (C). 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
0.086
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.12
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T;T
Eigen
Benign
0.028
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.81
.;T
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
-0.88
N;N
PhyloP100
1.7
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.43
N;N
REVEL
Benign
0.27
Sift
Benign
0.18
T;T
Sift4G
Benign
0.18
T;T
Polyphen
0.97
D;D
Vest4
0.90
MVP
0.69
MPC
0.030
ClinPred
0.070
T
GERP RS
5.8
Varity_R
0.24
gMVP
0.89
Mutation Taster
=84/16
polymorphism

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

Other links and lift over

dbSNP: rs377337647; hg19: chr8-71570108; API