rs767923145

Variant names:

• chr15-63122140-C-G
• rs767923145
• NM_032857.5:c.269C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-63122140-C-G
• chr15-63122140-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032857.5(LACTB):​c.269C>G​(p.Pro90Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,348,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.676
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08586252).

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.269C>G	p.Pro90Arg	missense	Exon 1 of 6	NP_116246.2
	LACTB	NM_171846.4		c.269C>G	p.Pro90Arg	missense	Exon 1 of 5	NP_741982.1	P83111-2
	LACTB	NM_001288585.2		c.269C>G	p.Pro90Arg	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.269C>G	p.Pro90Arg	missense	Exon 1 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.269C>G	p.Pro90Arg	missense	Exon 1 of 5	ENSP00000392956.2	P83111-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000107 AC: 1 AN: 93482 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000299

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000111 AC: 15 AN: 1348606 Hom.: 0 Cov.: 35 AF XY: 0.0000105 AC XY: 7 AN XY: 665440

African (AFR) AF: 0.0000363 AC: 1 AN: 27540

American (AMR) AF: 0.00 AC: 0 AN: 30752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23606

East Asian (EAS) AF: 0.0000316 AC: 1 AN: 31678

South Asian (SAS) AF: 0.00 AC: 0 AN: 76756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4218

European-Non Finnish (NFE) AF: 0.0000122 AC: 13 AN: 1064908

Other (OTH) AF: 0.00 AC: 0 AN: 56116

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000436 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000222 AC: 2

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	Benign	0.071
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.4
DANN	Benign	0.74
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.68
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.042
Sift	Benign	0.79	T
Sift4G	Benign	0.27	T
Polyphen		0.93	P
Vest4		0.25
MutPred		0.22		Loss of glycosylation at P90 (P = 0.0127)
MVP		0.39
MPC		0.41
ClinPred		0.082	T
GERP RS		-0.45
PromoterAI		-0.0058	Neutral
Varity_R		0.018
gMVP		0.44
Mutation Taster		=99/1	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: rs767923145; hg19: chr15-63414339;