8-70661850-C-A

Position:

• chr8-70661850-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016027.3(LACTB2):​c.170G>T​(p.Ser57Ile) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LACTB2 NM_016027.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2800097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB2	NM_016027.3	c.170G>T	p.Ser57Ile	missense_variant	2/7	ENST00000276590.5	NP_057111.1
LACTB2-AS1	NR_038881.1	n.2287C>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB2	ENST00000276590.5	c.170G>T	p.Ser57Ile	missense_variant	2/7	1	NM_016027.3	ENSP00000276590	P1
LACTB2-AS1	ENST00000499227.6	n.2287C>A		non_coding_transcript_exon_variant	4/4	1
LACTB2	ENST00000522447.5	c.170G>T	p.Ser57Ile	missense_variant	2/8	2		ENSP00000428801	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.170G>T (p.S57I) alteration is located in exon 2 (coding exon 2) of the LACTB2 gene. This alteration results from a G to T substitution at nucleotide position 170, causing the serine (S) at amino acid position 57 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Uncertain	0.67	D;D
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.053
Sift	Benign	0.069	T;T
Sift4G	Benign	0.079	T;T
Polyphen		0.022	B;B
Vest4		0.21
MutPred		0.39		Gain of ubiquitination at K60 (P = 0.0851);Gain of ubiquitination at K60 (P = 0.0851);
MVP		0.64
MPC		0.031
ClinPred		0.88	D
GERP RS		0.92
Varity_R		0.45
gMVP		0.75

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: chr8-71574085;