chr15-63121944-C-A

Variant names:

• chr15-63121944-C-A
• rs34297800
• NM_032857.5:c.73C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032857.5(LACTB):​c.73C>A​(p.Arg25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000317 in 1,260,386 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21572867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LACTB	NM_032857.5	c.73C>A	p.Arg25Ser	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.73C>A	p.Arg25Ser	missense_variant	Exon 1 of 6	1	NM_032857.5	ENSP00000261893.4
LACTB	ENST00000413507.3	c.73C>A	p.Arg25Ser	missense_variant	Exon 1 of 5	1		ENSP00000392956.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000319 AC: 2 AN: 62784 Hom.: 0 AF XY: 0.0000546 AC XY: 2 AN XY: 36640

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: 0.000127

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000311

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000317 AC: 4 AN: 1260386 Hom.: 0 Cov.: 35 AF XY: 0.00000323 AC XY: 2 AN XY: 618644

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: 0.0000522

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.78e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000926 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0095	T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.054
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.56	T;T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.10
Sift	Benign	0.050	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.96	D;.
Vest4		0.22
MutPred		0.38		Gain of glycosylation at R25 (P = 0.0062);Gain of glycosylation at R25 (P = 0.0062);
MVP		0.57
MPC		0.39
ClinPred		0.28	T
GERP RS		3.1
Varity_R		0.15
gMVP		0.52

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: rs34297800; hg19: chr15-63414143;