NM_005276.4:c.42-209C>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005276.4(GPD1):​c.42-209C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00903 in 707,786 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0093 (37 hom.)
• Consequence: GPD1 NM_005276.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.225
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 12-50104365-C-A is Benign according to our data. Variant chr12-50104365-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1215556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00791 (1205/152266) while in subpopulation NFE AF = 0.0142 (966/68004). AF 95% confidence interval is 0.0135. There are 11 homozygotes in GnomAd4. There are 557 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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>A		intron	N/A	NP_005267.2
	GPD1	NM_001257199.2		c.42-209C>A		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>A		intron	N/A	ENSP00000301149.3	P21695-1
	GPD1	ENST00000942603.1		c.42-209C>A		intron	N/A	ENSP00000612662.1
	GPD1	ENST00000872078.1		c.42-209C>A		intron	N/A	ENSP00000542137.1

Frequencies

GnomAD3 genomes AF: 0.00791 AC: 1204 AN: 152148 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00348

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00672 AC: 909 AN: 135306 AF XY: 0.00637

Gnomad AFR exome AF: 0.00108

Gnomad AMR exome AF: 0.00233

Gnomad ASJ exome AF: 0.00796

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00453

Gnomad NFE exome AF: 0.0128

Gnomad OTH exome AF: 0.00757

GnomAD4 exome AF: 0.00934 AC: 5188 AN: 555520 Hom.: 37 Cov.: 4 AF XY: 0.00906 AC XY: 2721 AN XY: 300470

African (AFR) AF: 0.00183 AC: 29 AN: 15806

American (AMR) AF: 0.00288 AC: 100 AN: 34668

Ashkenazi Jewish (ASJ) AF: 0.00825 AC: 165 AN: 20006

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

South Asian (SAS) AF: 0.00319 AC: 198 AN: 62114

European-Finnish (FIN) AF: 0.00582 AC: 220 AN: 37790

Middle Eastern (MID) AF: 0.00315 AC: 12 AN: 3810

European-Non Finnish (NFE) AF: 0.0132 AC: 4201 AN: 318616

Other (OTH) AF: 0.00859 AC: 263 AN: 30632

GnomAD4 genome AF: 0.00791 AC: 1205 AN: 152266 Hom.: 11 Cov.: 32 AF XY: 0.00748 AC XY: 557 AN XY: 74450

African (AFR) AF: 0.00272 AC: 113 AN: 41564

American (AMR) AF: 0.00183 AC: 28 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4822

European-Finnish (FIN) AF: 0.00348 AC: 37 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0142 AC: 966 AN: 68004

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.0107 Hom.: 3

Bravo AF: 0.00715

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.0
DANN	Benign	0.78
PhyloP100		0.23
PromoterAI		0.0046	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;