Genetic Variant LACTB:p.Lys316Ile (chr15-63127684-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032857.5(LACTB):c.947A>T(p.Lys316Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000507 in 1,576,422 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

LACTB
NM_032857.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.32

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:

RPS27L (HGNC:18476): (ribosomal protein S27 like) This gene encodes a protein sharing 96% amino acid similarity with ribosomal protein S27, which suggests the encoded protein may be a component of the 40S ribosomal subunit. [provided by RefSeq, Jul 2008]

RPS27L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LACTB	NM_032857.5 link	c.947A>T	p.Lys316Ile	missense_variant	Exon 4 of 6	ENST00000261893.9	NP_116246.2	P83111-1
LACTB	NM_171846.4 link	c.947A>T	p.Lys316Ile	missense_variant	Exon 4 of 5		NP_741982.1	P83111-2
LACTB	NM_001288585.2 link	c.947A>T	p.Lys316Ile	missense_variant	Exon 4 of 5		NP_001275514.1	P83111
LACTB	XM_047432128.1 link	c.947A>T	p.Lys316Ile	missense_variant	Exon 4 of 6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LACTB	ENST00000261893.9 link	c.947A>T	p.Lys316Ile	missense_variant	Exon 4 of 6	1	NM_032857.5	ENSP00000261893.4	P83111-1
LACTB	ENST00000413507.3 link	c.947A>T	p.Lys316Ile	missense_variant	Exon 4 of 5	1		ENSP00000392956.2	P83111-2
RPS27L	ENST00000559763.1 link	n.96-1664T>A		intron_variant	Intron 1 of 1	3
LACTB	ENST00000557972.1 link	c.*91A>T		downstream_gene_variant		2		ENSP00000454085.1	H0YNN5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000430

AC:

AN:

232522

Hom.:

AF XY:

0.00000789

AC XY:

AN XY:

126770

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:

0.0000368

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000492

AC:

AN:

1424208

Hom.:

Cov.:

AF XY:

0.00000564

AC XY:

AN XY:

709190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000791

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000368

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

1.0

D;.

Vest4

0.63

MutPred

0.64

Loss of methylation at K316 (P = 0.0011);Loss of methylation at K316 (P = 0.0011);

MVP

0.77

MPC

1.5

ClinPred

0.98

GERP RS

5.9

Varity_R

0.79

gMVP

0.78

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over