8-70669101-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016027.3(LACTB2):​c.20G>A​(p.Arg7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

LACTB2
NM_016027.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15029383).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LACTB2NM_016027.3 linkuse as main transcriptc.20G>A p.Arg7His missense_variant 1/7 ENST00000276590.5 NP_057111.1 Q53H82A0A024R811

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LACTB2ENST00000276590.5 linkuse as main transcriptc.20G>A p.Arg7His missense_variant 1/71 NM_016027.3 ENSP00000276590.4 Q53H82
LACTB2ENST00000522447.5 linkuse as main transcriptc.20G>A p.Arg7His missense_variant 1/82 ENSP00000428801.1 Q53H82

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 10, 2024The c.20G>A (p.R7H) alteration is located in exon 1 (coding exon 1) of the LACTB2 gene. This alteration results from a G to A substitution at nucleotide position 20, causing the arginine (R) at amino acid position 7 to be replaced by a histidine (H). 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
0.15
BayesDel_addAF
Uncertain
0.031
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
14
DANN
Uncertain
0.98
DEOGEN2
Benign
0.21
T;T
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.82
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.63
.;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Uncertain
-0.16
T
MutationAssessor
Benign
1.7
L;L
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.29
Sift
Benign
0.20
T;T
Sift4G
Benign
0.14
T;T
Polyphen
0.013
B;B
Vest4
0.24
MutPred
0.45
Loss of MoRF binding (P = 0.0185);Loss of MoRF binding (P = 0.0185);
MVP
0.64
MPC
0.030
ClinPred
0.23
T
GERP RS
-0.28
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.36
gMVP
0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-71581336; API