rs780641230

Variant names:

• chr8-70657829-T-A
• rs780641230
• NM_016027.3:c.340A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-70657829-T-A
• chr8-70657829-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016027.3(LACTB2):​c.340A>T​(p.Ile114Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LACTB2 NM_016027.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43

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)

ACMG classification

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=0.25043228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LACTB2	NM_016027.3	c.340A>T	p.Ile114Leu	missense_variant	Exon 3 of 7	ENST00000276590.5	NP_057111.1
LACTB2-AS1	NR_038881.1	n.582-2316T>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LACTB2	ENST00000276590.5	c.340A>T	p.Ile114Leu	missense_variant	Exon 3 of 7	1	NM_016027.3	ENSP00000276590.4
LACTB2-AS1	ENST00000499227.6	n.582-2316T>A		intron_variant	Intron 3 of 3	1
LACTB2	ENST00000522447.5	c.340A>T	p.Ile114Leu	missense_variant	Exon 3 of 8	2		ENSP00000428801.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459082 Hom.: 0 Cov.: 28 AF XY: 0.00000275 AC XY: 2 AN XY: 726080

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.63	.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.24
Sift	Benign	0.54	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0050	B;B
Vest4		0.46
MutPred		0.49		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.60
MPC		0.027
ClinPred		0.74	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.71

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

LitVar

Other links and lift over

dbSNP: rs780641230; hg19: chr8-71570064;