dbSNP rs371617943: GPAT2:p.Tyr680Cys (chr2-96023316-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001321527.2(GPAT2):c.2039A>G(p.Tyr680Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

GPAT2
NM_001321527.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.343

Publications

0 publications found

Variant links:

Genes affected

GPAT2 (HGNC:27168): (glycerol-3-phosphate acyltransferase 2, mitochondrial) Enables glycerol-3-phosphate O-acyltransferase activity. Predicted to be involved in several processes, including glycerol-3-phosphate metabolic process; glycerolipid biosynthetic process; and piRNA biosynthetic process. Predicted to be located in mitochondrial outer membrane. Predicted to be active in mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPAT2 links:

ENSG00000291176 (HGNC:):

ENSG00000291176 links:

FAHD2CP (HGNC:44135): (fumarylacetoacetate hydrolase domain containing 2C, pseudogene)

FAHD2CP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.124997765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPAT2	NM_001321527.2 link	c.2039A>G	p.Tyr680Cys	missense_variant	Exon 18 of 22	ENST00000434632.6	NP_001308456.1	Q6NUI2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPAT2	ENST00000434632.6 link	c.2039A>G	p.Tyr680Cys	missense_variant	Exon 18 of 22	5	NM_001321527.2	ENSP00000389395.2		Q6NUI2-4

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000401

AC:

AN:

249356

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000179

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000612

AC:

AN:

1111988

Other (OTH)

AF:

0.0000497

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000525

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41588

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000142

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 11, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2021A>G (p.Y674C) alteration is located in exon 18 (coding exon 17) of the GPAT2 gene. This alteration results from a A to G substitution at nucleotide position 2021, causing the tyrosine (Y) at amino acid position 674 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.016

T;T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.71

.;T;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

N;N;.

PhyloP100

0.34

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.89

N;N;N

REVEL

Benign

0.070

Sift

Benign

0.16

T;T;T

Sift4G

Uncertain

0.046

D;D;D

Polyphen

0.0010

B;B;B

Vest4

0.17

MVP

0.57

MPC

1.3

ClinPred

0.057

GERP RS

0.23

Varity_R

0.093

gMVP

0.17

Mutation Taster

=86/14

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over