15-63121917-G-C

Variant names:

• chr15-63121917-G-C
• rs34925488
• NM_032857.5:c.46G>C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_032857.5(LACTB):​c.46G>C​(p.Gly16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000789 in 1,266,964 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 Benign (no stars).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.22

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]

LOC107984798 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15721643).
• BP6: Variant 15-63121917-G-C is Benign according to our data. Variant chr15-63121917-G-C is described in ClinVar as [Benign]. Clinvar id is 208871.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LACTB	NM_032857.5	c.46G>C	p.Gly16Arg	missense_variant	Exon 1 of 6	ENST00000261893.9	NP_116246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.46G>C	p.Gly16Arg	missense_variant	Exon 1 of 6	1	NM_032857.5	ENSP00000261893.4
LACTB	ENST00000413507.3	c.46G>C	p.Gly16Arg	missense_variant	Exon 1 of 5	1		ENSP00000392956.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.89e-7 AC: 1 AN: 1266964 Hom.: 0 Cov.: 35 AF XY: 0.00000160 AC XY: 1 AN XY: 623508

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000470

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Abnormality of neuronal migration Benign:1

Oct 31, 2014

Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0086	T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.44	T;T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.010	N;N
REVEL	Benign	0.056
Sift	Benign	0.48	T;T
Sift4G	Uncertain	0.038	D;D
Polyphen		0.73	P;.
Vest4		0.13
MutPred		0.23		Gain of methylation at G16 (P = 0.012);Gain of methylation at G16 (P = 0.012);
MVP		0.44
MPC		0.40
ClinPred		0.32	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.065
gMVP		0.27

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

Other links and lift over

dbSNP: rs34925488; hg19: chr15-63414116;