12-50105281-C-T

Position:

• chr12-50105281-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005276.4(GPD1):​c.220-267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 504,606 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (7 hom.)
• Consequence: GPD1 NM_005276.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.396

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-50105281-C-T is Benign according to our data. Variant chr12-50105281-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1216010.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1646/152344) while in subpopulation AFR AF= 0.0377 (1568/41562). AF 95% confidence interval is 0.0362. There are 30 homozygotes in gnomad4. There are 765 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD1	NM_005276.4	c.220-267C>T		intron_variant		ENST00000301149.8	NP_005267.2
GPD1	NM_001257199.2	c.220-336C>T		intron_variant			NP_001244128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD1	ENST00000301149.8	c.220-267C>T		intron_variant		1	NM_005276.4	ENSP00000301149	P1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1643 AN: 152226 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00765

GnomAD4 exome AF: 0.00147 AC: 518 AN: 352262 Hom.: 7 Cov.: 2 AF XY: 0.00119 AC XY: 218 AN XY: 182984

Gnomad4 AFR exome AF: 0.0388

Gnomad4 AMR exome AF: 0.00249

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000322

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000236

Gnomad4 OTH exome AF: 0.00214

GnomAD4 genome AF: 0.0108 AC: 1646 AN: 152344 Hom.: 30 Cov.: 32 AF XY: 0.0103 AC XY: 765 AN XY: 74496

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.00372

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00316 Hom.: 2

Bravo AF: 0.0126

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.1
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs116427406; hg19: chr12-50499064;