Variant 15-63122140-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032857.5(LACTB):c.269C>G(p.Pro90Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,348,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

LACTB
NM_032857.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.676

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 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=0.08586252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5 linkuse as main transcript	c.269C>G	p.Pro90Arg	missense_variant	1/6	ENST00000261893.9	NP_116246.2	P83111-1
LACTB	NM_171846.4 linkuse as main transcript	c.269C>G	p.Pro90Arg	missense_variant	1/5		NP_741982.1	P83111-2
LACTB	NM_001288585.2 linkuse as main transcript	c.269C>G	p.Pro90Arg	missense_variant	1/5		NP_001275514.1	P83111
LACTB	XM_047432128.1 linkuse as main transcript	c.269C>G	p.Pro90Arg	missense_variant	1/6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9 linkuse as main transcript	c.269C>G	p.Pro90Arg	missense_variant	1/6	1	NM_032857.5	ENSP00000261893.4		P83111-1
LACTB	ENST00000413507.3 linkuse as main transcript	c.269C>G	p.Pro90Arg	missense_variant	1/5	1		ENSP00000392956.2		P83111-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000107

AC:

AN:

93482

Hom.:

AF XY:

0.00

AC XY:

AN XY:

53218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000299

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1348606

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

665440

show subpopulations

Gnomad4 AFR exome

AF:

0.0000363

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000316

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000122

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000436

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000222

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.269C>G (p.P90R) alteration is located in exon 1 (coding exon 1) of the LACTB gene. This alteration results from a C to G substitution at nucleotide position 269, causing the proline (P) at amino acid position 90 to be replaced by an arginine (R). 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

0.071

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.4

DANN

Benign

0.74

DEOGEN2

Benign

0.0059

T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.59

T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.62

N;N

REVEL

Benign

0.042

Sift

Benign

0.79

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.93

P;.

Vest4

0.25

MutPred

0.22

Loss of glycosylation at P90 (P = 0.0127);Loss of glycosylation at P90 (P = 0.0127);

MVP

0.39

MPC

0.41

ClinPred

0.082

GERP RS

-0.45

Varity_R

0.018

gMVP

0.44

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