rs11558492

Variant names:

• chr1-231272345-A-C
• rs11558492
• NM_014236.4:c.1556A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-231272345-A-C
• chr1-231272345-A-G
• chr1-231272345-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014236.4(GNPAT):​c.1556A>C​(p.Asp519Ala) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D519G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNPAT NM_014236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• glyceronephosphate O-acyltransferase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• rhizomelic chondrodysplasia punctata type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16870797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNPAT	NM_014236.4	c.1556A>C	p.Asp519Ala	missense_variant	Exon 11 of 16	ENST00000366647.9	NP_055051.1
GNPAT	NM_001316350.2	c.1373A>C	p.Asp458Ala	missense_variant	Exon 10 of 15		NP_001303279.1
GNPAT	XM_005273313.5	c.1553A>C	p.Asp518Ala	missense_variant	Exon 11 of 16		XP_005273370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPAT	ENST00000366647.9	c.1556A>C	p.Asp519Ala	missense_variant	Exon 11 of 16	1	NM_014236.4	ENSP00000355607.4
GNPAT	ENST00000416000.1	c.1526A>C	p.Asp509Ala	missense_variant	Exon 11 of 13	5		ENSP00000411640.1
GNPAT	ENST00000644483.1	n.*1242A>C		non_coding_transcript_exon_variant	Exon 12 of 17			ENSP00000496537.1
GNPAT	ENST00000644483.1	n.*1242A>C		3_prime_UTR_variant	Exon 12 of 17			ENSP00000496537.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Uncertain	0.42	T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		1.9
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.11
Sift	Benign	0.19	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.0040	B;.
Vest4		0.28
MutPred		0.48		Gain of catalytic residue at D519 (P = 0.1668);.;
MVP		0.50
MPC		0.31
ClinPred		0.50	D
GERP RS		-0.26
Varity_R		0.066
gMVP		0.26
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11558492; hg19: chr1-231408091;