1-231266156-G-T

Position:

• chr1-231266156-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000366647.9(GNPAT):​c.915G>T​(p.Glu305Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. E305E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNPAT ENST00000366647.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNPAT	NM_014236.4	c.915G>T	p.Glu305Asp	missense_variant	7/16	ENST00000366647.9	NP_055051.1
GNPAT	NM_001316350.2	c.732G>T	p.Glu244Asp	missense_variant	6/15		NP_001303279.1
GNPAT	XM_005273313.5	c.912G>T	p.Glu304Asp	missense_variant	7/16		XP_005273370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNPAT	ENST00000366647.9	c.915G>T	p.Glu305Asp	missense_variant	7/16	1	NM_014236.4	ENSP00000355607	P1
GNPAT	ENST00000416000.1	c.885G>T	p.Glu295Asp	missense_variant	7/13	5		ENSP00000411640
GNPAT	ENST00000492459.1	n.23G>T		non_coding_transcript_exon_variant	1/4	2
GNPAT	ENST00000644483.1	c.*601G>T		3_prime_UTR_variant, NMD_transcript_variant	8/17			ENSP00000496537

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.91	D;D
Eigen	Benign	0.18
Eigen_PC	Benign	0.056
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	3.1	M;.
MutationTaster	Benign	3.3e-7	P;P
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.75
MutPred		0.70		Gain of glycosylation at S306 (P = 0.1081);.;
MVP		0.59
MPC		0.81
ClinPred		1.0	D
GERP RS		3.2
Varity_R		0.62
gMVP		0.76

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

Other links and lift over

dbSNP: rs574553; hg19: chr1-231401902;