15-63121944-C-T

Position:

• chr15-63121944-C-T

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.73C>T​(p.Arg25Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,412,632 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts 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: 1.20

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=0.0020201504).
• BP6: Variant 15-63121944-C-T is Benign according to our data. Variant chr15-63121944-C-T is described in ClinVar as [Benign]. Clinvar id is 776909.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.73C>T	p.Arg25Cys	missense_variant	1/6	ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.73C>T	p.Arg25Cys	missense_variant	1/5		NP_741982.1
LACTB	NM_001288585.2	c.73C>T	p.Arg25Cys	missense_variant	1/5		NP_001275514.1
LACTB	XM_047432128.1	c.73C>T	p.Arg25Cys	missense_variant	1/6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.73C>T	p.Arg25Cys	missense_variant	1/6	1	NM_032857.5	ENSP00000261893	P1
LACTB	ENST00000413507.3	c.73C>T	p.Arg25Cys	missense_variant	1/5	1		ENSP00000392956

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2609 AN: 152142 Hom.: 70 Cov.: 34

Gnomad AFR AF: 0.0587

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: 0.00641

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00440 AC: 276 AN: 62784 Hom.: 4 AF XY: 0.00333 AC XY: 122 AN XY: 36640

Gnomad AFR exome AF: 0.0617

Gnomad AMR exome AF: 0.00411

Gnomad ASJ exome AF: 0.000425

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000254

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000683

Gnomad OTH exome AF: 0.00368

GnomAD4 exome AF: 0.00190 AC: 2394 AN: 1260380 Hom.: 60 Cov.: 35 AF XY: 0.00172 AC XY: 1066 AN XY: 618644

Gnomad4 AFR exome AF: 0.0612

Gnomad4 AMR exome AF: 0.00461

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.0000326

Gnomad4 NFE exome AF: 0.000404

Gnomad4 OTH exome AF: 0.00476

GnomAD4 genome AF: 0.0172 AC: 2617 AN: 152252 Hom.: 70 Cov.: 34 AF XY: 0.0163 AC XY: 1213 AN XY: 74448

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000721

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0100 Hom.: 2

Bravo AF: 0.0195

ESP6500AA AF: 0.0500 AC: 141

ESP6500EA AF: 0.00113 AC: 7

ExAC AF: 0.00369 AC: 399

Asia WGS AF: 0.00579 AC: 20 AN: 3468

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	0.28
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.061
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.73	T;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	0.97	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.085
Sift	Benign	0.082	T;T
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.19
MVP		0.48
MPC		0.52
ClinPred		0.013	T
GERP RS		3.1
Varity_R		0.12
gMVP		0.50

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: rs34297800; hg19: chr15-63414143;