Variant chr15-63121944-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

Variant links:

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]

LACTB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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
LACTB	NM_032857.5 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/6	ENST00000261893.9
LACTB	NM_171846.4 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/5
LACTB	NM_001288585.2 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/5
LACTB	XM_047432128.1 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LACTB	ENST00000261893.9 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/6	1	NM_032857.5	P1	P83111-1
LACTB	ENST00000413507.3 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/5	1			P83111-2

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2609

AN:

152142

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00333

AC XY:

122

AN XY:

36640

show subpopulations

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.:

Cov.:

AF XY:

0.00172

AC XY:

1066

AN XY:

618644

show subpopulations

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.:

Cov.:

AF XY:

0.0163

AC XY:

1213

AN XY:

74448

show subpopulations

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.:

Bravo

AF:

0.0195

ESP6500AA

AF:

0.0500

AC:

141

ESP6500EA

AF:

0.00113

AC:

ExAC

AF:

0.00369

AC:

399

Asia WGS

AF:

0.00579

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.061

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.73

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

0.97

D;D

PrimateAI

Pathogenic

0.82

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over