Genetic Variant GPAM:p.Asp399Asp (chr10-112166426-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001244949.2(GPAM):c.1197T>C(p.Asp399Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,602,358 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 111 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 100 hom. )

Consequence

GPAM
NM_001244949.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.117

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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 10-112166426-A-G is Benign according to our data. Variant chr10-112166426-A-G is described in ClinVar as [Benign]. Clinvar id is 776543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.117 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPAM	NM_001244949.2 link	c.1197T>C	p.Asp399Asp	synonymous_variant	Exon 12 of 22	ENST00000348367.9	NP_001231878.1	Q9HCL2Q8N1G6Q86T70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPAM	ENST00000348367.9 link	c.1197T>C	p.Asp399Asp	synonymous_variant	Exon 12 of 22	1	NM_001244949.2	ENSP00000265276.4		Q9HCL2
GPAM	ENST00000369425.5 link	c.1197T>C	p.Asp399Asp	synonymous_variant	Exon 12 of 19	1		ENSP00000358433.1		Q5VW52

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

3063

AN:

152144

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0699

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00511

AC:

1286

AN:

251418

AF XY:

0.00368

show subpopulations

Gnomad AFR exome

AF:

0.0706

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00200

AC:

2902

AN:

1450096

Hom.:

100

Cov.:

AF XY:

0.00173

AC XY:

1247

AN XY:

722354

show subpopulations

Gnomad4 AFR exome

AF:

0.0716

AC:

2375

AN:

33178

Gnomad4 AMR exome

AF:

0.00335

AC:

150

AN:

44716

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26064

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39628

Gnomad4 SAS exome

AF:

0.000151

AC:

AN:

86016

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53410

Gnomad4 NFE exome

AF:

0.0000999

AC:

110

AN:

1101360

Gnomad4 Remaining exome

AF:

0.00397

AC:

238

AN:

59976

Heterozygous variant carriers

128

256

384

512

640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0201

AC:

3062

AN:

152262

Hom.:

111

Cov.:

AF XY:

0.0198

AC XY:

1475

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0697

AC:

0.0696678

AN:

0.0696678

Gnomad4 AMR

AF:

0.00830

AC:

0.00829957

AN:

0.00829957

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000622

AC:

0.000621891

AN:

0.000621891

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000162

AC:

0.000161731

AN:

0.000161731

Gnomad4 OTH

AF:

0.0128

AC:

0.012772

AN:

0.012772

Heterozygous variant carriers

149

297

446

594

743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00968

Hom.:

Bravo

AF:

0.0233

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

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

- -

Jul 23, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.1

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

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

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