chr15-63121878-C-T

Variant names:

• chr15-63121878-C-T
• rs771795019
• NM_032857.5:c.7C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032857.5(LACTB):​c.7C>T​(p.Arg3Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000242 in 1,241,816 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: 0.0000024 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032857.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACTB	NM_032857.5	MANE Select	c.7C>T	p.Arg3Trp	missense	Exon 1 of 6	NP_116246.2
	LACTB	NM_171846.4		c.7C>T	p.Arg3Trp	missense	Exon 1 of 5	NP_741982.1	P83111-2
	LACTB	NM_001288585.2		c.7C>T	p.Arg3Trp	missense	Exon 1 of 5	NP_001275514.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACTB	ENST00000261893.9	TSL:1 MANE Select	c.7C>T	p.Arg3Trp	missense	Exon 1 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.7C>T	p.Arg3Trp	missense	Exon 1 of 5	ENSP00000392956.2	P83111-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000242 AC: 3 AN: 1241816 Hom.: 0 Cov.: 35 AF XY: 0.00000164 AC XY: 1 AN XY: 608090

African (AFR) AF: 0.00 AC: 0 AN: 25688

American (AMR) AF: 0.00 AC: 0 AN: 17568

Ashkenazi Jewish (ASJ) AF: 0.0000554 AC: 1 AN: 18064

East Asian (EAS) AF: 0.00 AC: 0 AN: 29552

South Asian (SAS) AF: 0.00 AC: 0 AN: 54104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4506

European-Non Finnish (NFE) AF: 0.00000198 AC: 2 AN: 1011706

Other (OTH) AF: 0.00 AC: 0 AN: 50682

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Benign	0.078
Eigen_PC	Benign	0.011
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.44		Loss of disorder (P = 0)
MVP		0.78
MPC		1.0
ClinPred		0.77	D
GERP RS		3.1
PromoterAI		0.24	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.35
gMVP		0.61
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs771795019; hg19: chr15-63414077;