10-112153464-T-C

Position:

• chr10-112153464-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244949.2(GPAM):​c.*86A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,604,694 control chromosomes in the GnomAD database, including 409,275 homozygotes. 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: 𝑓 0.69 (36006 hom., cov: 30)
  • Exomes 𝑓: 0.72 (373269 hom.)
• Consequence: GPAM NM_001244949.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596

Genes affected

GPAM (HGNC:24865): (glycerol-3-phosphate acyltransferase, mitochondrial) This gene encodes a mitochondrial enzyme which prefers saturated fatty acids as its substrate for the synthesis of glycerolipids. This metabolic pathway's first step is catalyzed by the encoded enzyme. Two forms for this enzyme exist, one in the mitochondria and one in the endoplasmic reticulum. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPAM	NM_001244949.2	c.*86A>G		3_prime_UTR_variant	22/22	ENST00000348367.9	NP_001231878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPAM	ENST00000348367	c.*86A>G		3_prime_UTR_variant	22/22	1	NM_001244949.2	ENSP00000265276.4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104389 AN: 151762 Hom.: 35994 Cov.: 30

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.716 AC: 1039494 AN: 1452814 Hom.: 373269 Cov.: 44 AF XY: 0.717 AC XY: 518456 AN XY: 722868

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.708

Gnomad4 ASJ exome AF: 0.567

Gnomad4 EAS exome AF: 0.753

Gnomad4 SAS exome AF: 0.815

Gnomad4 FIN exome AF: 0.654

Gnomad4 NFE exome AF: 0.715

Gnomad4 OTH exome AF: 0.711

GnomAD4 genome AF: 0.688 AC: 104441 AN: 151880 Hom.: 36006 Cov.: 30 AF XY: 0.686 AC XY: 50926 AN XY: 74224

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.675

Alfa AF: 0.692 Hom.: 64277

Bravo AF: 0.683

Asia WGS AF: 0.782 AC: 2720 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.3
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2297991; hg19: chr10-113913222;