rs143205045

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The ENST00000366647.9(GNPAT):ā€‹c.1212T>Cā€‹(p.Ala404=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,042 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A404A) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.0010 ( 0 hom., cov: 32)
Exomes š‘“: 0.0014 ( 3 hom. )

Consequence

GNPAT
ENST00000366647.9 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.137
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 1-231267836-T-C is Benign according to our data. Variant chr1-231267836-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 260360.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=4}.
BP7
Synonymous conserved (PhyloP=-0.137 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00102 (156/152320) while in subpopulation NFE AF= 0.00172 (117/68026). AF 95% confidence interval is 0.00147. There are 0 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GNPATNM_014236.4 linkuse as main transcriptc.1212T>C p.Ala404= synonymous_variant 9/16 ENST00000366647.9 NP_055051.1
GNPATNM_001316350.2 linkuse as main transcriptc.1029T>C p.Ala343= synonymous_variant 8/15 NP_001303279.1
GNPATXM_005273313.5 linkuse as main transcriptc.1209T>C p.Ala403= synonymous_variant 9/16 XP_005273370.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GNPATENST00000366647.9 linkuse as main transcriptc.1212T>C p.Ala404= synonymous_variant 9/161 NM_014236.4 ENSP00000355607 P1O15228-1
GNPATENST00000416000.1 linkuse as main transcriptc.1182T>C p.Ala394= synonymous_variant 9/135 ENSP00000411640
GNPATENST00000492459.1 linkuse as main transcriptn.320T>C non_coding_transcript_exon_variant 3/42
GNPATENST00000644483.1 linkuse as main transcriptc.*898T>C 3_prime_UTR_variant, NMD_transcript_variant 10/17 ENSP00000496537

Frequencies

GnomAD3 genomes
AF:
0.00102
AC:
156
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00172
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000819
AC:
206
AN:
251436
Hom.:
0
AF XY:
0.000787
AC XY:
107
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.000665
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00149
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00142
AC:
2069
AN:
1461722
Hom.:
3
Cov.:
31
AF XY:
0.00136
AC XY:
990
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.000760
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.00175
Gnomad4 OTH exome
AF:
0.00104
GnomAD4 genome
AF:
0.00102
AC:
156
AN:
152320
Hom.:
0
Cov.:
32
AF XY:
0.000819
AC XY:
61
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00172
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00119
Hom.:
0
Bravo
AF:
0.00110
EpiCase
AF:
0.00115
EpiControl
AF:
0.00154

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2022GNPAT: BP4, BP7 -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -
Rhizomelic chondrodysplasia punctata Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Rhizomelic chondrodysplasia punctata type 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesSep 05, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
6.7
DANN
Benign
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs143205045; hg19: chr1-231403582; API