chr15-63127658-A-T

Position:

• chr15-63127658-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032857.5(LACTB):​c.921A>T​(p.Leu307Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0880

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]

RPS27L (HGNC:):

ACMG classification

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=0.283929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5	c.921A>T	p.Leu307Phe	missense_variant	4/6	ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.921A>T	p.Leu307Phe	missense_variant	4/5		NP_741982.1
LACTB	NM_001288585.2	c.921A>T	p.Leu307Phe	missense_variant	4/5		NP_001275514.1
LACTB	XM_047432128.1	c.921A>T	p.Leu307Phe	missense_variant	4/6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.921A>T	p.Leu307Phe	missense_variant	4/6	1	NM_032857.5	ENSP00000261893.4
LACTB	ENST00000413507.3	c.921A>T	p.Leu307Phe	missense_variant	4/5	1		ENSP00000392956.2
RPS27L	ENST00000559763.1	n.96-1638T>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.921A>T (p.L307F) alteration is located in exon 4 (coding exon 4) of the LACTB gene. This alteration results from a A to T substitution at nucleotide position 921, causing the leucine (L) at amino acid position 307 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	0.55
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.97	D;.
Vest4		0.41
MutPred		0.59		Gain of ubiquitination at K309 (P = 0.0797);Gain of ubiquitination at K309 (P = 0.0797);
MVP		0.49
MPC		0.89
ClinPred		0.97	D
GERP RS		3.5
Varity_R		0.23
gMVP		0.55

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.

Other links and lift over

hg19: chr15-63419857;