8-41620981-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_StrongBP6_Moderate

The NM_178819.4(GPAT4):c.1351A>G(p.Lys451Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000193 in 1,551,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GPAT4
NM_178819.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.50

Variant links:

Genes affected

GPAT4 (HGNC:20880): (glycerol-3-phosphate acyltransferase 4) Lysophosphatidic acid acyltransferases (EC 2.3.1.51) catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA). LPA and PA are involved in signal transduction and lipid biosynthesis.[supplied by OMIM, Apr 2004]

GPAT4 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, GPAT4

BP4

Computational evidence support a benign effect (MetaRNN=0.02894339).

BP6

Variant 8-41620981-A-G is Benign according to our data. Variant chr8-41620981-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3101134.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPAT4	NM_178819.4 linkuse as main transcript	c.1351A>G	p.Lys451Glu	missense_variant	13/13	ENST00000396987.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPAT4	ENST00000396987.7 linkuse as main transcript	c.1351A>G	p.Lys451Glu	missense_variant	13/13	1	NM_178819.4	P1
	ENST00000581909.1 linkuse as main transcript	n.522T>C		non_coding_transcript_exon_variant	1/2	5
GPAT4	ENST00000518628.1 linkuse as main transcript	n.650A>G		non_coding_transcript_exon_variant	3/3	3
GPAT4	ENST00000521349.1 linkuse as main transcript	n.450A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1398930

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Benign

0.40

DEOGEN2

Benign

0.072

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.44

M_CAP

Benign

0.0063

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.49

REVEL

Benign

0.061

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.075

MutPred

0.25

Loss of MoRF binding (P = 2e-04);

MVP

0.081

MPC

1.0

ClinPred

0.16

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.093

gMVP

0.41

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