15-63127684-A-C

Variant names:

• chr15-63127684-A-C
• NM_032857.5:c.947A>C

Variant summary

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

The NM_032857.5(LACTB):​c.947A>C​(p.Lys316Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,424,208 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: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.32

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: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]

ACMG classification

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	c.947A>C	p.Lys316Thr	missense_variant	Exon 4 of 6	ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.947A>C	p.Lys316Thr	missense_variant	Exon 4 of 5		NP_741982.1
LACTB	NM_001288585.2	c.947A>C	p.Lys316Thr	missense_variant	Exon 4 of 5		NP_001275514.1
LACTB	XM_047432128.1	c.947A>C	p.Lys316Thr	missense_variant	Exon 4 of 6		XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.947A>C	p.Lys316Thr	missense_variant	Exon 4 of 6	1	NM_032857.5	ENSP00000261893.4
LACTB	ENST00000413507.3	c.947A>C	p.Lys316Thr	missense_variant	Exon 4 of 5	1		ENSP00000392956.2
RPS27L	ENST00000559763.1	n.96-1664T>G		intron_variant	Intron 1 of 1	3
LACTB	ENST00000557972.1	c.*91A>C		downstream_gene_variant		2		ENSP00000454085.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424208 Hom.: 0 Cov.: 26 AF XY: 0.00000141 AC XY: 1 AN XY: 709190

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: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.034	D;D
Polyphen		1.0	D;.
Vest4		0.57
MutPred		0.46		Loss of methylation at K316 (P = 0.0011);Loss of methylation at K316 (P = 0.0011);
MVP		0.82
MPC		1.2
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.43
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.

Other links and lift over

hg19: chr15-63419883;