rs1060499861

Variant names:

• chr3-32138715-C-CGAGTT
• rs1060499861
• NM_015141.4:c.354_355insGAGTT

Variant summary

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

The NM_015141.4(GPD1L):​c.354_355insGAGTT​(p.Thr119GlufsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPD1L NM_015141.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• Publications: 0 publications found

Genes affected

GPD1L (HGNC:28956): (glycerol-3-phosphate dehydrogenase 1 like) The protein encoded by this gene catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate. The encoded protein is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Defects in this gene are a cause of Brugada syndrome type 2 (BRS2) as well as sudden infant death syndrome (SIDS). [provided by RefSeq, Jul 2010]

GPD1L Gene-Disease associations (from GenCC):

• Brugada syndrome 2

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

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_015141.4. 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
	GPD1L	NM_015141.4	MANE Select	c.354_355insGAGTT	p.Thr119GlufsTer8	frameshift	Exon 3 of 8	NP_055956.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD1L	ENST00000282541.10	TSL:1 MANE Select	c.354_355insGAGTT	p.Thr119GlufsTer8	frameshift	Exon 3 of 8	ENSP00000282541.6
	GPD1L	ENST00000902849.1		c.351_352insGAGTT	p.Thr118GlufsTer8	frameshift	Exon 3 of 8	ENSP00000572908.1
	GPD1L	ENST00000902848.1		c.354_355insGAGTT	p.Thr119GlufsTer8	frameshift	Exon 3 of 7	ENSP00000572907.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1060499861; hg19: chr3-32180207;