19-39607299-C-A

Variant names:

• chr19-39607299-C-A
• rs748246666
• NM_013268.3:c.380C>A

Variant summary

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

The NM_013268.3(LGALS13):​c.380C>A​(p.Ser127*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LGALS13 NM_013268.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 0 publications found

Genes affected

LGALS13 (HGNC:15449): (galectin 13) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. The protein encoded by this gene has lysophospholipase activity. It is composed of two identical subunits which are held together by disulfide bonds. This protein has structural similarity to several members of the beta-galactoside-binding S-type lectin family. [provided by RefSeq, Jul 2008]

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_013268.3. 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
	LGALS13	NM_013268.3	MANE Select	c.380C>A	p.Ser127*	stop_gained	Exon 4 of 4	NP_037400.1	Q9UHV8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS13	ENST00000221797.5	TSL:1 MANE Select	c.380C>A	p.Ser127*	stop_gained	Exon 4 of 4	ENSP00000221797.3	Q9UHV8
	LGALS13	ENST00000600546.1	TSL:2	n.374C>A		non_coding_transcript_exon	Exon 2 of 2
	LGALS13	ENST00000600141.1	TSL:3	c.*40C>A		downstream_gene	N/A	ENSP00000470928.1	M0R015

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461600 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111766

Other (OTH) AF: 0.00 AC: 0 AN: 60388

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	26
DANN	Benign	0.69
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.0041	N
PhyloP100		-0.059
Vest4		0.63
GERP RS		-1.5
Mutation Taster		=42/158	disease causing

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: rs748246666; hg19: chr19-40097939;