Genetic Variant NM_001244949.2:c.*2587T>C (chr10-112150963-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001244949.2(GPAM):c.*2587T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 983,986 control chromosomes in the GnomAD database, including 258,178 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 0.71 ( 38473 hom., cov: 32)

Exomes 𝑓: 0.73 ( 219705 hom. )

Consequence

GPAM
NM_001244949.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.750

Publications

33 publications found

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:

ENSG00000295048 (HGNC:):

ENSG00000295048 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPAM	NM_001244949.2 link	c.*2587T>C		3_prime_UTR_variant	Exon 22 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.*2587T>C		3_prime_UTR_variant	Exon 22 of 22	1	NM_001244949.2	ENSP00000265276.4		Q9HCL2
ENSG00000295048	ENST00000727646.1 link	n.249-4938A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107967

AN:

151978

Hom.:

38454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.728

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.735

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.712

Gnomad OTH

AF:

0.692

GnomAD4 exome

AF:

0.726

AC:

604338

AN:

831890

Hom.:

219705

Cov.:

AF XY:

0.727

AC XY:

279283

AN XY:

384224

show subpopulations

African (AFR)

AF:

0.745

AC:

11737

AN:

15744

American (AMR)

AF:

0.673

AC:

664

AN:

986

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

2907

AN:

5136

East Asian (EAS)

AF:

0.755

AC:

2735

AN:

3622

South Asian (SAS)

AF:

0.815

AC:

13389

AN:

16424

European-Finnish (FIN)

AF:

0.685

AC:

415

AN:

606

Middle Eastern (MID)

AF:

0.655

AC:

1060

AN:

1618

European-Non Finnish (NFE)

AF:

0.725

AC:

551466

AN:

760500

Other (OTH)

AF:

0.733

AC:

19965

AN:

27254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

7508

15015

22523

30030

37538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18732

37464

56196

74928

93660

<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:

0.710

AC:

108027

AN:

152096

Hom.:

38473

Cov.:

AF XY:

0.709

AC XY:

52704

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.728

AC:

30184

AN:

41478

American (AMR)

AF:

0.681

AC:

10416

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.577

AC:

2004

AN:

3472

East Asian (EAS)

AF:

0.736

AC:

3802

AN:

5168

South Asian (SAS)

AF:

0.827

AC:

3988

AN:

4820

European-Finnish (FIN)

AF:

0.670

AC:

7068

AN:

10556

Middle Eastern (MID)

AF:

0.592

AC:

173

AN:

292

European-Non Finnish (NFE)

AF:

0.712

AC:

48402

AN:

68002

Other (OTH)

AF:

0.696

AC:

1469

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1618

3236

4853

6471

8089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.705

Hom.:

103587

Bravo

AF:

0.707

Asia WGS

AF:

0.786

AC:

2734

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.54

(source)

DANN

Benign

0.45

PhyloP100

-0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over