15-63122195-C-A

Variant names:

• chr15-63122195-C-A
• rs1400065234
• NM_032857.5:c.324C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_032857.5(LACTB):​c.324C>A​(p.Ile108Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,391,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LACTB NM_032857.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 1 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 (BayesDel_noAF=-0.12).
• BP7: Synonymous conserved (PhyloP=-0.62 with no splicing effect.

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.324C>A	p.Ile108Ile	synonymous	Exon 1 of 6	NP_116246.2
	LACTB	NM_171846.4		c.324C>A	p.Ile108Ile	synonymous	Exon 1 of 5	NP_741982.1	P83111-2
	LACTB	NM_001288585.2		c.324C>A	p.Ile108Ile	synonymous	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.324C>A	p.Ile108Ile	synonymous	Exon 1 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.324C>A	p.Ile108Ile	synonymous	Exon 1 of 5	ENSP00000392956.2	P83111-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1391944 Hom.: 0 Cov.: 35 AF XY: 0.00000145 AC XY: 1 AN XY: 688808

African (AFR) AF: 0.00 AC: 0 AN: 31286

American (AMR) AF: 0.00 AC: 0 AN: 36808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24762

East Asian (EAS) AF: 0.00 AC: 0 AN: 35942

South Asian (SAS) AF: 0.00 AC: 0 AN: 80066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4660

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1086256

Other (OTH) AF: 0.00 AC: 0 AN: 57976

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	11
DANN	Benign	0.95
PhyloP100		-0.62
PromoterAI		-0.059	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1400065234; hg19: chr15-63414394;