rs201152084

Variant names:

• chr3-32106722-C-A
• rs201152084
• NM_015141.4:c.11C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-32106722-C-A
• chr3-32106722-C-T

Variant summary

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

The NM_015141.4(GPD1L):​c.11C>A​(p.Ala4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,411,212 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: GPD1L NM_015141.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25404721).

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.11C>A	p.Ala4Glu	missense	Exon 1 of 8	NP_055956.1	Q8N335

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD1L	ENST00000282541.10	TSL:1 MANE Select	c.11C>A	p.Ala4Glu	missense	Exon 1 of 8	ENSP00000282541.6	Q8N335
	GPD1L	ENST00000902849.1		c.11C>A	p.Ala4Glu	missense	Exon 1 of 8	ENSP00000572908.1
	GPD1L	ENST00000902848.1		c.11C>A	p.Ala4Glu	missense	Exon 1 of 7	ENSP00000572907.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1411212 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 701758

⚠️ 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: 29256

American (AMR) AF: 0.00 AC: 0 AN: 39470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24560

East Asian (EAS) AF: 0.00 AC: 0 AN: 34010

South Asian (SAS) AF: 0.00 AC: 0 AN: 81030

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5548

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088002

Other (OTH) AF: 0.00 AC: 0 AN: 57868

⚠️ 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.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.088
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.050
Sift	Benign	0.58	T
Sift4G	Benign	0.34	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.39		Gain of solvent accessibility (P = 0.0261)
MVP		0.66
MPC		0.52
ClinPred		0.71	D
GERP RS		4.4
PromoterAI		-0.034	Neutral
Varity_R		0.29
gMVP		0.47
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs201152084; hg19: chr3-32148214;