NM_001244949.2:c.127A>G

Variant names:

• chr10-112180571-T-C
• rs2792751
• NM_001244949.2:c.127A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244949.2(GPAM):​c.127A>G​(p.Ile43Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 1,608,874 control chromosomes in the GnomAD database, including 434,741 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45662 hom., cov: 32)
  • Exomes 𝑓: 0.73 (389079 hom.)
• Consequence: GPAM NM_001244949.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.25
• Publications: 69 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.5698847E-7).
• BP6: Variant 10-112180571-T-C is Benign according to our data. Variant chr10-112180571-T-C is described in ClinVar as Benign. ClinVar VariationId is 1285804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPAM	NM_001244949.2	c.127A>G	p.Ile43Val	missense_variant	Exon 4 of 22	ENST00000348367.9	NP_001231878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPAM	ENST00000348367.9	c.127A>G	p.Ile43Val	missense_variant	Exon 4 of 22	1	NM_001244949.2	ENSP00000265276.4
GPAM	ENST00000369425.5	c.127A>G	p.Ile43Val	missense_variant	Exon 4 of 19	1		ENSP00000358433.1
GPAM	ENST00000480130.5	n.464A>G		non_coding_transcript_exon_variant	Exon 4 of 4	2
GPAM	ENST00000498541.1	n.332A>G		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116644 AN: 151988 Hom.: 45610 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.728

GnomAD2 exomes AF: 0.734 AC: 184441 AN: 251212 AF XY: 0.731

Gnomad AFR exome AF: 0.931

Gnomad AMR exome AF: 0.726

Gnomad ASJ exome AF: 0.580

Gnomad EAS exome AF: 0.725

Gnomad FIN exome AF: 0.676

Gnomad NFE exome AF: 0.711

Gnomad OTH exome AF: 0.715

GnomAD4 exome AF: 0.729 AC: 1061827 AN: 1456768 Hom.: 389079 Cov.: 35 AF XY: 0.729 AC XY: 528740 AN XY: 725044

African (AFR) AF: 0.937 AC: 31313 AN: 33408

American (AMR) AF: 0.722 AC: 32258 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 14901 AN: 26092

East Asian (EAS) AF: 0.753 AC: 29842 AN: 39644

South Asian (SAS) AF: 0.817 AC: 70390 AN: 86172

European-Finnish (FIN) AF: 0.677 AC: 36133 AN: 53380

Middle Eastern (MID) AF: 0.679 AC: 3912 AN: 5764

European-Non Finnish (NFE) AF: 0.721 AC: 798877 AN: 1107382

Other (OTH) AF: 0.734 AC: 44201 AN: 60222

GnomAD4 genome AF: 0.768 AC: 116755 AN: 152106 Hom.: 45662 Cov.: 32 AF XY: 0.765 AC XY: 56868 AN XY: 74362

African (AFR) AF: 0.927 AC: 38474 AN: 41518

American (AMR) AF: 0.698 AC: 10679 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3817 AN: 5178

South Asian (SAS) AF: 0.829 AC: 3995 AN: 4820

European-Finnish (FIN) AF: 0.669 AC: 7056 AN: 10548

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48483 AN: 67966

Other (OTH) AF: 0.732 AC: 1545 AN: 2110

Alfa AF: 0.716 Hom.: 122317

Bravo AF: 0.772

TwinsUK AF: 0.731 AC: 2711

ALSPAC AF: 0.720 AC: 2774

ESP6500AA AF: 0.926 AC: 4081

ESP6500EA AF: 0.707 AC: 6076

ExAC AF: 0.742 AC: 90130

Asia WGS AF: 0.805 AC: 2797 AN: 3478

EpiCase AF: 0.702

EpiControl AF: 0.697

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29083407, 32640185) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.4
DANN	Benign	0.14
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.071	T;T
MetaRNN	Benign	7.6e-7	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.6	N;.
PhyloP100		1.2
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.15	N;N
REVEL	Benign	0.042
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.028
MPC		0.23
ClinPred		0.0000096	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.021
gMVP		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2792751; hg19: chr10-113940329; COSMIC: COSV62081535;