rs2792751

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.77 ( 45662 hom., cov: 32)

Exomes 𝑓: 0.73 ( 389079 hom. )

Consequence

GPAM
NM_001244949.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.25

Variant links:

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]

GPAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 link	c.127A>G	p.Ile43Val	missense_variant	Exon 4 of 22	ENST00000348367.9	NP_001231878.1	Q9HCL2Q8N1G6Q86T70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPAM	ENST00000348367.9 link	c.127A>G	p.Ile43Val	missense_variant	Exon 4 of 22	1	NM_001244949.2	ENSP00000265276.4	Q9HCL2
GPAM	ENST00000369425.5 link	c.127A>G	p.Ile43Val	missense_variant	Exon 4 of 19	1		ENSP00000358433.1	Q5VW52
GPAM	ENST00000480130.5 link	n.464A>G		non_coding_transcript_exon_variant	Exon 4 of 4	2
GPAM	ENST00000498541.1 link	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.:

show subpopulations

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

GnomAD3 exomes

AF:

0.734

AC:

184441

AN:

251212

Hom.:

68492

AF XY:

0.731

AC XY:

99271

AN XY:

135786

show subpopulations

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 SAS exome

AF:

0.828

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.:

AF XY:

0.729

AC XY:

528740

AN XY:

725044

show subpopulations

Gnomad4 AFR exome

AF:

0.937

Gnomad4 AMR exome

AF:

0.722

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.753

Gnomad4 SAS exome

AF:

0.817

Gnomad4 FIN exome

AF:

0.677

Gnomad4 NFE exome

AF:

0.721

Gnomad4 OTH exome

AF:

0.734

GnomAD4 genome

AF:

0.768

AC:

116755

AN:

152106

Hom.:

45662

Cov.:

AF XY:

0.765

AC XY:

56868

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.927

Gnomad4 AMR

AF:

0.698

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.737

Gnomad4 SAS

AF:

0.829

Gnomad4 FIN

AF:

0.669

Gnomad4 NFE

AF:

0.713

Gnomad4 OTH

AF:

0.732

Alfa

AF:

0.709

Hom.:

88307

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

LINK: link

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

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

LIST_S2

Benign

0.071

T;T

MetaRNN

Benign

7.6e-7

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.6

N;.

PrimateAI

Benign

0.48

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

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.021

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over