10-112175621-T-C

Variant names:

• chr10-112175621-T-C
• rs10787428
• NM_001244949.2:c.392A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244949.2(GPAM):​c.392A>G​(p.Glu131Gly) variant causes a missense change. The variant allele was found at a frequency of 0.59 in 1,599,440 control chromosomes in the GnomAD database, including 280,251 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 0.55 (23494 hom., cov: 32)
  • Exomes 𝑓: 0.59 (256757 hom.)
• Consequence: GPAM NM_001244949.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.11
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5096874E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244949.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPAM	NM_001244949.2	MANE Select	c.392A>G	p.Glu131Gly	missense	Exon 6 of 22	NP_001231878.1
	GPAM	NM_020918.6		c.392A>G	p.Glu131Gly	missense	Exon 6 of 22	NP_065969.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPAM	ENST00000348367.9	TSL:1 MANE Select	c.392A>G	p.Glu131Gly	missense	Exon 6 of 22	ENSP00000265276.4
	GPAM	ENST00000369425.5	TSL:1	c.392A>G	p.Glu131Gly	missense	Exon 6 of 19	ENSP00000358433.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84000 AN: 151862 Hom.: 23483 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.535

GnomAD2 exomes AF: 0.563 AC: 141463 AN: 251388 AF XY: 0.566

Gnomad AFR exome AF: 0.506

Gnomad AMR exome AF: 0.491

Gnomad ASJ exome AF: 0.515

Gnomad EAS exome AF: 0.578

Gnomad FIN exome AF: 0.525

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.569

GnomAD4 exome AF: 0.594 AC: 859349 AN: 1447460 Hom.: 256757 Cov.: 29 AF XY: 0.594 AC XY: 428069 AN XY: 721044

African (AFR) AF: 0.509 AC: 16900 AN: 33214

American (AMR) AF: 0.490 AC: 21918 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 13228 AN: 26038

East Asian (EAS) AF: 0.616 AC: 24408 AN: 39626

South Asian (SAS) AF: 0.613 AC: 52723 AN: 85964

European-Finnish (FIN) AF: 0.526 AC: 28068 AN: 53350

Middle Eastern (MID) AF: 0.517 AC: 2964 AN: 5736

European-Non Finnish (NFE) AF: 0.605 AC: 664306 AN: 1098876

Other (OTH) AF: 0.581 AC: 34834 AN: 59952

GnomAD4 genome AF: 0.553 AC: 84045 AN: 151980 Hom.: 23494 Cov.: 32 AF XY: 0.550 AC XY: 40820 AN XY: 74272

African (AFR) AF: 0.507 AC: 21012 AN: 41406

American (AMR) AF: 0.498 AC: 7603 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1793 AN: 3464

East Asian (EAS) AF: 0.593 AC: 3064 AN: 5164

South Asian (SAS) AF: 0.629 AC: 3029 AN: 4818

European-Finnish (FIN) AF: 0.515 AC: 5434 AN: 10556

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40398 AN: 67984

Other (OTH) AF: 0.538 AC: 1132 AN: 2106

Alfa AF: 0.574 Hom.: 89461

Bravo AF: 0.545

TwinsUK AF: 0.621 AC: 2303

ALSPAC AF: 0.609 AC: 2346

ESP6500AA AF: 0.504 AC: 2220

ESP6500EA AF: 0.588 AC: 5054

ExAC AF: 0.566 AC: 68773

Asia WGS AF: 0.575 AC: 2003 AN: 3478

EpiCase AF: 0.588

EpiControl AF: 0.572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.00045	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.011	D
Polyphen		0.25	B
Vest4		0.23
MPC		0.44
ClinPred		0.010	T
GERP RS		5.1
Varity_R		0.35
gMVP		0.47
Mutation Taster		=83/17	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10787428; hg19: chr10-113935379; COSMIC: COSV62080161; COSMIC: COSV62080161;