Variant chr15-63122195-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000261893.9(LACTB):c.324C>G(p.Ile108Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,544,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

LACTB
ENST00000261893.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.620

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3657474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5 linkuse as main transcript	c.324C>G	p.Ile108Met	missense_variant	1/6	ENST00000261893.9	NP_116246.2	P83111-1
LACTB	NM_171846.4 linkuse as main transcript	c.324C>G	p.Ile108Met	missense_variant	1/5		NP_741982.1	P83111-2
LACTB	NM_001288585.2 linkuse as main transcript	c.324C>G	p.Ile108Met	missense_variant	1/5		NP_001275514.1	P83111
LACTB	XM_047432128.1 linkuse as main transcript	c.324C>G	p.Ile108Met	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.324C>G	p.Ile108Met	missense_variant	1/6	1	NM_032857.5	ENSP00000261893.4		P83111-1
LACTB	ENST00000413507.3 linkuse as main transcript	c.324C>G	p.Ile108Met	missense_variant	1/5	1		ENSP00000392956.2		P83111-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1391944

Hom.:

Cov.:

AF XY:

0.00000726

AC XY:

AN XY:

688808

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000362

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.21e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 31, 2023

The c.324C>G (p.I108M) 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 324, causing the isoleucine (I) at amino acid position 108 to be replaced by a methionine (M). 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

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

0.11

Eigen_PC

Benign

-0.014

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.050

T;T

Polyphen

1.0

D;.

Vest4

0.28

MutPred

0.41

Gain of disorder (P = 0.0777);Gain of disorder (P = 0.0777);

MVP

0.51

MPC

1.1

ClinPred

0.93

GERP RS

1.8

Varity_R

0.30

gMVP

0.66

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