rs2255141

Positions:

• chr10-112174128-A-G
• chr10-112174128-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.414-283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,098 control chromosomes in the GnomAD database, including 46,012 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 0.77 (46012 hom., cov: 32)
• Consequence: GPAM NM_001244949.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPAM	NM_001244949.2	c.414-283T>C		intron_variant		ENST00000348367.9	NP_001231878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPAM	ENST00000348367.9	c.414-283T>C		intron_variant		1	NM_001244949.2	ENSP00000265276	P1
GPAM	ENST00000369425.5	c.414-283T>C		intron_variant		1		ENSP00000358433

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117043 AN: 151982 Hom.: 45957 Cov.: 32

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.729

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.770 AC: 117157 AN: 152098 Hom.: 46012 Cov.: 32 AF XY: 0.768 AC XY: 57055 AN XY: 74336

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.732

Alfa AF: 0.713 Hom.: 45499

Bravo AF: 0.775

Asia WGS AF: 0.804 AC: 2793 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.33

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: rs2255141; hg19: chr10-113933886;