15-63121917-G-A

Position:

• chr15-63121917-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032857.5(LACTB):​c.46G>A​(p.Gly16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,419,246 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (70 hom., cov: 34)
  • Exomes 𝑓: 0.0019 (60 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025365055).
• BP6: Variant 15-63121917-G-A is Benign according to our data. Variant chr15-63121917-G-A is described in ClinVar as [Benign]. Clinvar id is 776908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5	c.46G>A	p.Gly16Arg	missense_variant	1/6	ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.46G>A	p.Gly16Arg	missense_variant	1/5		NP_741982.1
LACTB	NM_001288585.2	c.46G>A	p.Gly16Arg	missense_variant	1/5		NP_001275514.1
LACTB	XM_047432128.1	c.46G>A	p.Gly16Arg	missense_variant	1/6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.46G>A	p.Gly16Arg	missense_variant	1/6	1	NM_032857.5	ENSP00000261893.4
LACTB	ENST00000413507.3	c.46G>A	p.Gly16Arg	missense_variant	1/5	1		ENSP00000392956.2

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2611 AN: 152184 Hom.: 70 Cov.: 34

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00621

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00416 AC: 358 AN: 85998 Hom.: 5 AF XY: 0.00320 AC XY: 160 AN XY: 49994

Gnomad AFR exome AF: 0.0559

Gnomad AMR exome AF: 0.00475

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000274

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000682

Gnomad OTH exome AF: 0.00338

GnomAD4 exome AF: 0.00192 AC: 2429 AN: 1266954 Hom.: 60 Cov.: 35 AF XY: 0.00174 AC XY: 1084 AN XY: 623506

Gnomad4 AFR exome AF: 0.0610

Gnomad4 AMR exome AF: 0.00489

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000168

Gnomad4 FIN exome AF: 0.0000318

Gnomad4 NFE exome AF: 0.000412

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.0172 AC: 2619 AN: 152292 Hom.: 70 Cov.: 34 AF XY: 0.0163 AC XY: 1214 AN XY: 74454

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.00620

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00227 Hom.: 8

Bravo AF: 0.0195

ESP6500AA AF: 0.0475 AC: 130

ESP6500EA AF: 0.000338 AC: 2

ExAC AF: 0.00387 AC: 429

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0086	T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.44	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.010	N;N
REVEL	Benign	0.061
Sift	Benign	0.48	T;T
Sift4G	Uncertain	0.038	D;D
Polyphen		0.86	P;.
Vest4		0.13
MutPred		0.23		Gain of methylation at G16 (P = 0.012);Gain of methylation at G16 (P = 0.012);
MVP		0.44
MPC		0.40
ClinPred		0.013	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.065
gMVP		0.27

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: rs34925488; hg19: chr15-63414116;