1-231267836-T-G

Variant names:

• chr1-231267836-T-G
• rs143205045
• NM_014236.4:c.1212T>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_014236.4(GNPAT):​c.1212T>G​(p.Ala404Ala) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A404A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNPAT NM_014236.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.137
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-231267836-T-G is Benign according to our data. Variant chr1-231267836-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2708279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.137 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPAT	NM_014236.4	MANE Select	c.1212T>G	p.Ala404Ala	synonymous	Exon 9 of 16	NP_055051.1
	GNPAT	NM_001316350.2		c.1029T>G	p.Ala343Ala	synonymous	Exon 8 of 15	NP_001303279.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPAT	ENST00000366647.9	TSL:1 MANE Select	c.1212T>G	p.Ala404Ala	synonymous	Exon 9 of 16	ENSP00000355607.4
	GNPAT	ENST00000416000.1	TSL:5	c.1182T>G	p.Ala394Ala	synonymous	Exon 9 of 13	ENSP00000411640.1
	GNPAT	ENST00000492459.1	TSL:2	n.320T>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.6
DANN	Benign	0.69
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs143205045; hg19: chr1-231403582;