rs574553

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014236.4(GNPAT):c.915G>A(p.Glu305Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,611,462 control chromosomes in the GnomAD database, including 260,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26814 hom., cov: 32)

Exomes 𝑓: 0.56 ( 233392 hom. )

Consequence

GNPAT
NM_014236.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

GNPAT (HGNC:4416): (glyceronephosphate O-acyltransferase) This gene encodes an enzyme located in the peroxisomal membrane which is essential to the synthesis of ether phospholipids. Mutations in this gene are associated with rhizomelic chondrodysplasia punctata. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

GNPAT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-231266156-G-A is Benign according to our data. Variant chr1-231266156-G-A is described in ClinVar as [Benign]. Clinvar id is 260363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-231266156-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNPAT	NM_014236.4 link	c.915G>A	p.Glu305Glu	synonymous_variant	Exon 7 of 16	ENST00000366647.9	NP_055051.1	O15228-1
GNPAT	NM_001316350.2 link	c.732G>A	p.Glu244Glu	synonymous_variant	Exon 6 of 15		NP_001303279.1	O15228-2
GNPAT	XM_005273313.5 link	c.912G>A	p.Glu304Glu	synonymous_variant	Exon 7 of 16		XP_005273370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPAT	ENST00000366647.9 link	c.915G>A	p.Glu305Glu	synonymous_variant	Exon 7 of 16	1	NM_014236.4	ENSP00000355607.4		O15228-1

Frequencies

GnomAD3 genomes

AF:

0.588

AC:

89380

AN:

151934

Hom.:

26756

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.621

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.541

Gnomad OTH

AF:

0.604

GnomAD3 exomes

AF:

0.570

AC:

143156

AN:

251224

Hom.:

41427

AF XY:

0.569

AC XY:

77275

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.693

Gnomad AMR exome

AF:

0.615

Gnomad ASJ exome

AF:

0.609

Gnomad EAS exome

AF:

0.597

Gnomad SAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.575

GnomAD4 exome

AF:

0.563

AC:

821393

AN:

1459410

Hom.:

233392

Cov.:

AF XY:

0.564

AC XY:

409864

AN XY:

726186

show subpopulations

Gnomad4 AFR exome

AF:

0.691

Gnomad4 AMR exome

AF:

0.613

Gnomad4 ASJ exome

AF:

0.611

Gnomad4 EAS exome

AF:

0.606

Gnomad4 SAS exome

AF:

0.621

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.555

Gnomad4 OTH exome

AF:

0.577

GnomAD4 genome

AF:

0.589

AC:

89487

AN:

152052

Hom.:

26814

Cov.:

AF XY:

0.584

AC XY:

43381

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.690

Gnomad4 AMR

AF:

0.608

Gnomad4 ASJ

AF:

0.627

Gnomad4 EAS

AF:

0.621

Gnomad4 SAS

AF:

0.621

Gnomad4 FIN

AF:

0.434

Gnomad4 NFE

AF:

0.541

Gnomad4 OTH

AF:

0.605

Alfa

AF:

0.569

Hom.:

18055

Bravo

AF:

0.605

Asia WGS

AF:

0.619

AC:

2154

AN:

3478

EpiCase

AF:

0.554

EpiControl

AF:

0.554

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rhizomelic chondrodysplasia punctata type 2

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Oct 20, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.5

DANN

Benign

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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