Variant 12-50104691-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BS1BS2

The NM_005276.4(GPD1):c.159C>A(p.Ile53Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000893 in 1,614,102 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 12 hom. )

Consequence

GPD1
NM_005276.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.76

Variant links:

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 links:

GPD1 (HGNC:):

GPD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.11).

BP6

Variant 12-50104691-C-A is Benign according to our data. Variant chr12-50104691-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 703255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-50104691-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.76 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00133 (202/152348) while in subpopulation AMR AF= 0.003 (46/15308). AF 95% confidence interval is 0.00231. There are 0 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD1	NM_005276.4 linkuse as main transcript	c.159C>A	p.Ile53Ile	synonymous_variant	2/8	ENST00000301149.8	NP_005267.2	P21695-1A0A024R138
GPD1	NM_001257199.2 linkuse as main transcript	c.159C>A	p.Ile53Ile	synonymous_variant	2/8		NP_001244128.1	P21695-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD1	ENST00000301149.8 linkuse as main transcript	c.159C>A	p.Ile53Ile	synonymous_variant	2/8	1	NM_005276.4	ENSP00000301149.3		P21695-1

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

203

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00173

AC:

436

AN:

251452

Hom.:

AF XY:

0.00172

AC XY:

234

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.0238

Gnomad EAS exome

AF:

0.00152

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000527

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.000848

AC:

1240

AN:

1461754

Hom.:

Cov.:

AF XY:

0.000858

AC XY:

624

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.0237

Gnomad4 EAS exome

AF:

0.000705

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000251

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.00133

AC:

202

AN:

152348

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00300

Gnomad4 ASJ

AF:

0.0274

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.00182

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000771

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 07, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	GPD1: BP4 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over