8-70640987-A-C

Variant names:

• chr8-70640987-A-C
• rs368252116
• NM_016027.3:c.656T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016027.3(LACTB2):​c.656T>G​(p.Ile219Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,486 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I219T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LACTB2 NM_016027.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081061065).

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.656T>G	p.Ile219Ser	missense	Exon 5 of 7	NP_057111.1	A0A024R811
	LACTB2-AS1	NR_038881.1		n.258-10826A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACTB2	ENST00000276590.5	TSL:1 MANE Select	c.656T>G	p.Ile219Ser	missense	Exon 5 of 7	ENSP00000276590.4	Q53H82
	LACTB2-AS1	ENST00000499227.6	TSL:1	n.258-10826A>C		intron	N/A
	LACTB2	ENST00000522447.5	TSL:2	c.656T>G	p.Ile219Ser	missense	Exon 5 of 8	ENSP00000428801.1	Q53H82

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457486 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724978

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.0000229 AC: 1 AN: 43706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39328

South Asian (SAS) AF: 0.00 AC: 0 AN: 85134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110690

Other (OTH) AF: 0.00 AC: 0 AN: 60184

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	0.058
DANN	Benign	0.66
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.74	N
PhyloP100		-0.15
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.25
Sift	Benign	0.71	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.46		Gain of disorder (P = 0.0011)
MVP		0.49
MPC		0.033
ClinPred		0.032	T
GERP RS		-5.6
Varity_R		0.13
gMVP		0.41
Mutation Taster		=78/22	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

Other links and lift over

dbSNP: rs368252116; hg19: chr8-71553222;