chr12-50104356-T-G

Position:

• chr12-50104356-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005276.4(GPD1):​c.42-218T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 705,434 control chromosomes in the GnomAD database, including 165,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37909 hom., cov: 31)
  • Exomes 𝑓: 0.67 (127472 hom.)
• Consequence: GPD1 NM_005276.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.458

Genes affected

GPD1 (HGNC:4455): (glycerol-3-phosphate dehydrogenase 1) This gene encodes a member of the NAD-dependent glycerol-3-phosphate dehydrogenase family. The encoded protein plays a critical role in carbohydrate and lipid metabolism by catalyzing the reversible conversion of dihydroxyacetone phosphate (DHAP) and reduced nicotine adenine dinucleotide (NADH) to glycerol-3-phosphate (G3P) and NAD+. The encoded cytosolic protein and mitochondrial glycerol-3-phosphate dehydrogenase also form a glycerol phosphate shuttle that facilitates the transfer of reducing equivalents from the cytosol to mitochondria. Mutations in this gene are a cause of transient infantile hypertriglyceridemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-50104356-T-G is Benign according to our data. Variant chr12-50104356-T-G is described in ClinVar as [Benign]. Clinvar id is 1249493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-50104356-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD1	NM_005276.4	c.42-218T>G		intron_variant		ENST00000301149.8	NP_005267.2
GPD1	NM_001257199.2	c.42-218T>G		intron_variant			NP_001244128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD1	ENST00000301149.8	c.42-218T>G		intron_variant		1	NM_005276.4	ENSP00000301149	P1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106639 AN: 151878 Hom.: 37859 Cov.: 31

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.674 AC: 373194 AN: 553438 Hom.: 127472 Cov.: 4 AF XY: 0.668 AC XY: 200011 AN XY: 299468

Gnomad4 AFR exome AF: 0.780

Gnomad4 AMR exome AF: 0.735

Gnomad4 ASJ exome AF: 0.800

Gnomad4 EAS exome AF: 0.874

Gnomad4 SAS exome AF: 0.607

Gnomad4 FIN exome AF: 0.692

Gnomad4 NFE exome AF: 0.644

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.702 AC: 106751 AN: 151996 Hom.: 37909 Cov.: 31 AF XY: 0.707 AC XY: 52513 AN XY: 74274

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.702

Alfa AF: 0.656 Hom.: 45534

Bravo AF: 0.710

Asia WGS AF: 0.714 AC: 2476 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs836178; hg19: chr12-50498139;