Variant chr15-63126954-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032857.5(LACTB):c.520C>T(p.Leu174Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,338 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LACTB
NM_032857.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

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/exons	MANE
LACTB	NM_032857.5 linkuse as main transcript	c.520C>T	p.Leu174Phe	missense_variant	3/6	ENST00000261893.9
LACTB	NM_171846.4 linkuse as main transcript	c.520C>T	p.Leu174Phe	missense_variant	3/5
LACTB	NM_001288585.2 linkuse as main transcript	c.520C>T	p.Leu174Phe	missense_variant	3/5
LACTB	XM_047432128.1 linkuse as main transcript	c.520C>T	p.Leu174Phe	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LACTB	ENST00000261893.9 linkuse as main transcript	c.520C>T	p.Leu174Phe	missense_variant	3/6	1	NM_032857.5	P1	P83111-1
LACTB	ENST00000413507.3 linkuse as main transcript	c.520C>T	p.Leu174Phe	missense_variant	3/5	1			P83111-2
LACTB	ENST00000557972.1 linkuse as main transcript	c.43C>T	p.Leu15Phe	missense_variant	2/3	2
RPS27L	ENST00000559763.1 linkuse as main transcript	n.96-934G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461338

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 16, 2023

The c.520C>T (p.L174F) alteration is located in exon 3 (coding exon 3) of the LACTB gene. This alteration results from a C to T substitution at nucleotide position 520, causing the leucine (L) at amino acid position 174 to be replaced by a phenylalanine (F). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

0.65

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.3

N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.045

D;D;D

Sift4G

Benign

0.072

T;T;D

Polyphen

0.96

D;.;.

Vest4

0.51

MutPred

0.64

Loss of MoRF binding (P = 0.1319);Loss of MoRF binding (P = 0.1319);.;

MVP

0.66

MPC

0.64

ClinPred

0.58

GERP RS

2.3

Varity_R

0.099

gMVP

0.74

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over