rs1129555

Positions:

• chr10-112150963-A-G
• chr10-112150963-A-T

Variant summary

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

The NM_001244949.2(GPAM):​c.*2587T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 983,986 control chromosomes in the GnomAD database, including 258,178 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 0.71 (38473 hom., cov: 32)
  • Exomes 𝑓: 0.73 (219705 hom.)
• Consequence: GPAM NM_001244949.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPAM	NM_001244949.2	c.*2587T>C		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	ENST00000348367.9	c.*2587T>C		3_prime_UTR_variant	22/22	1	NM_001244949.2	ENSP00000265276	P1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107967 AN: 151978 Hom.: 38454 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.692

GnomAD4 exome AF: 0.726 AC: 604338 AN: 831890 Hom.: 219705 Cov.: 21 AF XY: 0.727 AC XY: 279283 AN XY: 384224

Gnomad4 AFR exome AF: 0.745

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.755

Gnomad4 SAS exome AF: 0.815

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.733

GnomAD4 genome AF: 0.710 AC: 108027 AN: 152096 Hom.: 38473 Cov.: 32 AF XY: 0.709 AC XY: 52704 AN XY: 74348

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.696

Alfa AF: 0.700 Hom.: 62309

Bravo AF: 0.707

Asia WGS AF: 0.786 AC: 2734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.54
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1129555; hg19: chr10-113910721;