15-63122056-G-T

Position:

• chr15-63122056-G-T

Variant summary

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

The NM_032857.5(LACTB):​c.185G>T​(p.Gly62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,277,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16

Genes affected

LACTB (HGNC:16468): (lactamase beta) This gene encodes a mitochondrially-localized protein that has sequence similarity to prokaryotic beta-lactamases. Many of the residues responsible for beta-lactamase activity are not conserved in this protein, suggesting it may have a different enzymatic function. Increased expression of the related mouse gene was found to be associated with obesity. Alternative splicing results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Dec 2013]

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=0.21915808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5	c.185G>T	p.Gly62Val	missense_variant	1/6	ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.185G>T	p.Gly62Val	missense_variant	1/5		NP_741982.1
LACTB	NM_001288585.2	c.185G>T	p.Gly62Val	missense_variant	1/5		NP_001275514.1
LACTB	XM_047432128.1	c.185G>T	p.Gly62Val	missense_variant	1/6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.185G>T	p.Gly62Val	missense_variant	1/6	1	NM_032857.5	ENSP00000261893.4
LACTB	ENST00000413507.3	c.185G>T	p.Gly62Val	missense_variant	1/5	1		ENSP00000392956.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000157 AC: 2 AN: 1277326 Hom.: 0 Cov.: 35 AF XY: 0.00000319 AC XY: 2 AN XY: 626092

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: 0.0000156

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.68e-7

Gnomad4 OTH exome AF: 0.00

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

Aug 30, 2022

The c.185G>T (p.G62V) alteration is located in exon 1 (coding exon 1) of the LACTB gene. This alteration results from a G to T substitution at nucleotide position 185, causing the glycine (G) at amino acid position 62 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.74	T;T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.050	N;N
REVEL	Benign	0.077
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.17	T;D
Polyphen		0.36	B;.
Vest4		0.42
MutPred		0.35		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.53
MPC		0.43
ClinPred		0.60	D
GERP RS		2.9
Varity_R		0.12
gMVP		0.35

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: chr15-63414255;