rs959647146

Variant names:

• chr15-63122100-T-A
• rs959647146
• NM_032857.5:c.229T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-63122100-T-A
• chr15-63122100-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032857.5(LACTB):​c.229T>A​(p.Ser77Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,471,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.04
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038860947).

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.229T>A	p.Ser77Thr	missense	Exon 1 of 6	NP_116246.2
	LACTB	NM_171846.4		c.229T>A	p.Ser77Thr	missense	Exon 1 of 5	NP_741982.1	P83111-2
	LACTB	NM_001288585.2		c.229T>A	p.Ser77Thr	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.229T>A	p.Ser77Thr	missense	Exon 1 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.229T>A	p.Ser77Thr	missense	Exon 1 of 5	ENSP00000392956.2	P83111-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152028 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000439 AC: 3 AN: 68372 AF XY: 0.0000506

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000527

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000432 AC: 57 AN: 1319108 Hom.: 0 Cov.: 35 AF XY: 0.0000477 AC XY: 31 AN XY: 649288

African (AFR) AF: 0.00 AC: 0 AN: 26444

American (AMR) AF: 0.00 AC: 0 AN: 26636

Ashkenazi Jewish (ASJ) AF: 0.0000448 AC: 1 AN: 22298

East Asian (EAS) AF: 0.00 AC: 0 AN: 29244

South Asian (SAS) AF: 0.00 AC: 0 AN: 72154

European-Finnish (FIN) AF: 0.000310 AC: 10 AN: 32266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3896

European-Non Finnish (NFE) AF: 0.0000399 AC: 42 AN: 1051454

Other (OTH) AF: 0.0000731 AC: 4 AN: 54716

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152028 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74268

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000264

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	0.073
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.5
DANN	Benign	0.76
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.38	T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.0
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.010
Sift	Benign	0.54	T
Sift4G	Benign	0.061	T
Polyphen		0.0050	B
Vest4		0.076
MutPred		0.24		Loss of glycosylation at P78 (P = 0.2299)
MVP		0.21
MPC		0.31
ClinPred		0.018	T
GERP RS		0.078
PromoterAI		-0.00040	Neutral
Varity_R		0.10
gMVP		0.25
Mutation Taster		=98/2	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: rs959647146; hg19: chr15-63414299;