rs144877595

Variant names:

• chr3-32165835-G-A
• rs144877595
• NM_015141.4:c.981G>A
• GPD1L p.Val327Val

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015141.4(GPD1L):​c.981G>A​(p.Val327Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,601,564 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (3 hom.)
• Consequence: GPD1L NM_015141.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.45
• 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: Unknown, AD Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 3-32165835-G-A is Benign according to our data. Variant chr3-32165835-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.45 with no splicing effect.
• BS2: High AC in GnomAd4 at 276 AD,Unknown gene.

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.981G>A	p.Val327Val	synonymous	Exon 8 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.981G>A	p.Val327Val	synonymous	Exon 8 of 8	ENSP00000282541.6	Q8N335
	GPD1L	ENST00000902849.1		c.978G>A	p.Val326Val	synonymous	Exon 8 of 8	ENSP00000572908.1
	GPD1L	ENST00000902848.1		c.747G>A	p.Val249Val	synonymous	Exon 7 of 7	ENSP00000572907.1

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 270 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00623

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000529 AC: 133 AN: 251460 AF XY: 0.000419

Gnomad AFR exome AF: 0.00714

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000192 AC: 278 AN: 1449280 Hom.: 3 Cov.: 27 AF XY: 0.000190 AC XY: 137 AN XY: 721906

African (AFR) AF: 0.00672 AC: 223 AN: 33200

American (AMR) AF: 0.000313 AC: 14 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000698 AC: 6 AN: 86006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1100564

Other (OTH) AF: 0.000533 AC: 32 AN: 59982

GnomAD4 genome AF: 0.00181 AC: 276 AN: 152284 Hom.: 0 Cov.: 33 AF XY: 0.00185 AC XY: 138 AN XY: 74458

African (AFR) AF: 0.00635 AC: 264 AN: 41546

American (AMR) AF: 0.000523 AC: 8 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.00222

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Brugada syndrome (1)
-	-	1	Brugada syndrome 2 (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	GPD1L-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-2.4
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs144877595;

hg19: chr3-32207327;