rs72558073

Variant names:

• chr3-32146689-C-G
• rs72558073
• NM_015141.4:c.573C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-32146689-C-G
• chr3-32146689-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015141.4(GPD1L):​c.573C>G​(p.Thr191Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,334 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T191T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0056 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00060 (4 hom.)
• Consequence: GPD1L NM_015141.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.51
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-32146689-C-G is Benign according to our data. Variant chr3-32146689-C-G is described in ClinVar as Benign. ClinVar VariationId is 190763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.51 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00557 (848/152176) while in subpopulation AFR AF = 0.0188 (780/41514). AF 95% confidence interval is 0.0177. There are 9 homozygotes in GnomAd4. There are 403 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 848 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.573C>G	p.Thr191Thr	synonymous	Exon 5 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.573C>G	p.Thr191Thr	synonymous	Exon 5 of 8	ENSP00000282541.6	Q8N335
	GPD1L	ENST00000902849.1		c.570C>G	p.Thr190Thr	synonymous	Exon 5 of 8	ENSP00000572908.1
	GPD1L	ENST00000902848.1		c.573C>G	p.Thr191Thr	synonymous	Exon 5 of 7	ENSP00000572907.1

Frequencies

GnomAD3 genomes AF: 0.00554 AC: 842 AN: 152058 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00156 AC: 392 AN: 251452 AF XY: 0.00118

Gnomad AFR exome AF: 0.0214

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000597 AC: 872 AN: 1461158 Hom.: 4 Cov.: 29 AF XY: 0.000503 AC XY: 366 AN XY: 726942

African (AFR) AF: 0.0218 AC: 728 AN: 33460

American (AMR) AF: 0.00125 AC: 56 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111360

Other (OTH) AF: 0.00111 AC: 67 AN: 60372

GnomAD4 genome AF: 0.00557 AC: 848 AN: 152176 Hom.: 9 Cov.: 33 AF XY: 0.00542 AC XY: 403 AN XY: 74418

African (AFR) AF: 0.0188 AC: 780 AN: 41514

American (AMR) AF: 0.00380 AC: 58 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67998

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.000537 Hom.: 1

Bravo AF: 0.00708

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.22
DANN	Benign	0.83
PhyloP100		-5.5
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs72558073; hg19: chr3-32188181;