8-70661763-A-T

Variant names:

• chr8-70661763-A-T
• rs375034003
• NM_016027.3:c.257T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016027.3(LACTB2):​c.257T>A​(p.Ile86Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: LACTB2 NM_016027.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.96

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.961

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LACTB2	NM_016027.3	c.257T>A	p.Ile86Lys	missense_variant	Exon 2 of 7	ENST00000276590.5	NP_057111.1
LACTB2-AS1	NR_038881.1	n.2200A>T		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LACTB2	ENST00000276590.5	c.257T>A	p.Ile86Lys	missense_variant	Exon 2 of 7	1	NM_016027.3	ENSP00000276590.4
LACTB2-AS1	ENST00000499227.6	n.2200A>T		non_coding_transcript_exon_variant	Exon 4 of 4	1
LACTB2	ENST00000522447.5	c.257T>A	p.Ile86Lys	missense_variant	Exon 2 of 8	2		ENSP00000428801.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 249870 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135014

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460258 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726394

Gnomad4 AFR exome AF: 0.00

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: 0.00000810

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Pathogenic	0.85	D;D
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.99	D;D
Vest4		0.80
MVP		0.95
MPC		0.23
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.88
gMVP		0.97

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: rs375034003; hg19: chr8-71573998;