chr1-231262767-T-A

Variant names:

• chr1-231262767-T-A
• NM_014236.4:c.483T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014236.4(GNPAT):​c.483T>A​(p.Ser161Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GNPAT NM_014236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNPAT	NM_014236.4	c.483T>A	p.Ser161Arg	missense_variant	Exon 4 of 16	ENST00000366647.9	NP_055051.1
GNPAT	NM_001316350.2	c.300T>A	p.Ser100Arg	missense_variant	Exon 3 of 15		NP_001303279.1
GNPAT	XM_005273313.5	c.480T>A	p.Ser160Arg	missense_variant	Exon 4 of 16		XP_005273370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPAT	ENST00000366647.9	c.483T>A	p.Ser161Arg	missense_variant	Exon 4 of 16	1	NM_014236.4	ENSP00000355607.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454792 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 724274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.95	.;D;D
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.93
MutPred		0.78		.;Gain of helix (P = 0.132);.;
MVP		0.91
MPC		0.90
ClinPred		0.99	D
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-231398513;