chr8-70637868-G-A

Variant names:

• chr8-70637868-G-A
• rs774475856
• NM_016027.3:c.859C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016027.3(LACTB2):​c.859C>T​(p.His287Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,550,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H287L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: LACTB2 NM_016027.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.671
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039126635).

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.859C>T	p.His287Tyr	missense	Exon 7 of 7	NP_057111.1	A0A024R811
	LACTB2-AS1	NR_038881.1		n.258-13945G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACTB2	ENST00000276590.5	TSL:1 MANE Select	c.859C>T	p.His287Tyr	missense	Exon 7 of 7	ENSP00000276590.4	Q53H82
	LACTB2-AS1	ENST00000499227.6	TSL:1	n.258-13945G>A		intron	N/A
	LACTB2	ENST00000522447.5	TSL:2	c.859C>T	p.His287Tyr	missense	Exon 7 of 8	ENSP00000428801.1	Q53H82

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000137 AC: 3 AN: 218862 AF XY: 0.0000252

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000289

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000236 AC: 33 AN: 1398170 Hom.: 0 Cov.: 27 AF XY: 0.0000317 AC XY: 22 AN XY: 694694

African (AFR) AF: 0.00 AC: 0 AN: 30682

American (AMR) AF: 0.00 AC: 0 AN: 37228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24506

East Asian (EAS) AF: 0.00 AC: 0 AN: 37272

South Asian (SAS) AF: 0.00 AC: 0 AN: 73928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 0.0000306 AC: 33 AN: 1079760

Other (OTH) AF: 0.00 AC: 0 AN: 57486

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152082 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000828 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.0
DANN	Benign	0.72
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.67
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	0.65	T
Polyphen		0.10	B
Vest4		0.14
MVP		0.54
MPC		0.035
ClinPred		0.024	T
GERP RS		-6.2
Varity_R		0.16
gMVP		0.20
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs774475856; hg19: chr8-71550103;