12-50104365-C-G

Variant names:

• chr12-50104365-C-G
• rs71441319
• NM_005276.4:c.42-209C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005276.4(GPD1):​c.42-209C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 555,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: GPD1 NM_005276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 0 publications found

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]

GPD1 Gene-Disease associations (from GenCC):

• transient infantile hypertriglyceridemia and hepatosteatosis

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ENSG00000295262 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005276.4. 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
	GPD1	NM_005276.4	MANE Select	c.42-209C>G		intron	N/A	NP_005267.2
	GPD1	NM_001257199.2		c.42-209C>G		intron	N/A	NP_001244128.1	P21695-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD1	ENST00000301149.8	TSL:1 MANE Select	c.42-209C>G		intron	N/A	ENSP00000301149.3	P21695-1
	GPD1	ENST00000942603.1		c.42-209C>G		intron	N/A	ENSP00000612662.1
	GPD1	ENST00000872078.1		c.42-209C>G		intron	N/A	ENSP00000542137.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000180 AC: 1 AN: 555528 Hom.: 0 Cov.: 4 AF XY: 0.00000333 AC XY: 1 AN XY: 300474

African (AFR) AF: 0.00 AC: 0 AN: 15806

American (AMR) AF: 0.00 AC: 0 AN: 34670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20006

East Asian (EAS) AF: 0.00 AC: 0 AN: 32078

South Asian (SAS) AF: 0.00 AC: 0 AN: 62114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3810

European-Non Finnish (NFE) AF: 0.00000314 AC: 1 AN: 318622

Other (OTH) AF: 0.00 AC: 0 AN: 30632

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.2
DANN	Benign	0.69
PhyloP100		0.23
PromoterAI		0.016	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs71441319; hg19: chr12-50498148;