rs9835387

Variant names:

• chr3-32140269-C-T
• rs9835387
• NM_015141.4:c.408C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015141.4(GPD1L):​c.408C>T​(p.Asp136Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,640 control chromosomes in the GnomAD database, including 17,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2795 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14351 hom.)
• Consequence: GPD1L NM_015141.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.37
• Publications: 15 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 3-32140269-C-T is Benign according to our data. Variant chr3-32140269-C-T is described in ClinVar as Benign. ClinVar VariationId is 260571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

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.408C>T	p.Asp136Asp	synonymous	Exon 4 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.408C>T	p.Asp136Asp	synonymous	Exon 4 of 8	ENSP00000282541.6	Q8N335
	GPD1L	ENST00000902849.1		c.405C>T	p.Asp135Asp	synonymous	Exon 4 of 8	ENSP00000572908.1
	GPD1L	ENST00000902848.1		c.408C>T	p.Asp136Asp	synonymous	Exon 4 of 7	ENSP00000572907.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25981 AN: 151994 Hom.: 2792 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.123 AC: 30986 AN: 251324 AF XY: 0.123

Gnomad AFR exome AF: 0.303

Gnomad AMR exome AF: 0.0710

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.000761

Gnomad FIN exome AF: 0.0970

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.133 AC: 194805 AN: 1461528 Hom.: 14351 Cov.: 33 AF XY: 0.133 AC XY: 96939 AN XY: 727092

African (AFR) AF: 0.307 AC: 10290 AN: 33468

American (AMR) AF: 0.0795 AC: 3554 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3170 AN: 26132

East Asian (EAS) AF: 0.000630 AC: 25 AN: 39700

South Asian (SAS) AF: 0.138 AC: 11861 AN: 86246

European-Finnish (FIN) AF: 0.0955 AC: 5102 AN: 53416

Middle Eastern (MID) AF: 0.138 AC: 796 AN: 5768

European-Non Finnish (NFE) AF: 0.137 AC: 151915 AN: 1111692

Other (OTH) AF: 0.134 AC: 8092 AN: 60386

GnomAD4 genome AF: 0.171 AC: 25996 AN: 152112 Hom.: 2795 Cov.: 32 AF XY: 0.167 AC XY: 12430 AN XY: 74378

African (AFR) AF: 0.299 AC: 12394 AN: 41454

American (AMR) AF: 0.118 AC: 1802 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5174

South Asian (SAS) AF: 0.141 AC: 678 AN: 4812

European-Finnish (FIN) AF: 0.0957 AC: 1014 AN: 10600

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9154 AN: 68018

Other (OTH) AF: 0.159 AC: 335 AN: 2102

Alfa AF: 0.148 Hom.: 5793

Bravo AF: 0.177

Asia WGS AF: 0.0850 AC: 295 AN: 3478

EpiCase AF: 0.136

EpiControl AF: 0.137

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Brugada syndrome (1)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		1.4
Mutation Taster		=15/85	polymorphism (auto)

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: rs9835387; hg19: chr3-32181761; COSMIC: COSV56990087;